16163028, 2022, 19, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/adfm.202112902 by Spanish Cochrane National Provision (Ministerio de Sanidad), Wiley Online Library on [14/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Research Article www.afm-journal.de Antibacterial Films Based on MOF Composites that Release Iodine Passively or Upon Triggering by Near-Infrared Light Xu Han, Gerard Boix, Mateusz Balcerzak, Oscar Hernando Moriones, Mary Cano-Sarabia, Pilar Cortés, Neus Bastús, Victor Puntes, Montserrat Llagostera, Inhar Imaz,* and Daniel Maspoch* 1. Introduction Multidrug-resistant bacteria have become a global health problem for which new prophylactic strategies are now needed, including surface-coatings for Infectious diseases are a rapidly growing hospital spaces and medical equipment. This work reports the preparation threat to humanity. For instance, the cur- rent COVID-19 pandemic, caused by and functional validation of a metal-organic framework (MOF) based com- the virus SARS-CoV-2, has already killed posite for the triggered controlled release of iodine, an antimicrobial element over 37 60 000 people[1] and is taking a that does not generate resistance. It comprises beads of the iodophilic MOF devastating socioeconomic toll world- UiO-66 containing encapsulated gold nanorods (AuNRs) coated with a silica wide. Unfortunately, COVID-19 is only shell. Irradiation of the AuNRs with near-infrared light (NIR) provokes a one of countless pathogenic diseases put- ting public health at risk. A particularly photothermal effect and the resultant heat actively liberates the iodine. After menacing group of such diseases is the validating the performance of this composite, it is integrated into a polymer for nosocomial infections (also called hospital- the development of antibacterial films. This work assesses the adsorption of acquired infections), which are caused by iodine into these composite films, as well as its passive long-term release and bacteria, viruses, fungi, yeast, or para- active light-triggered. Finally, this work validates the antibacterial activity of the sites acquired in hospital by a patient who composite films in vitro against gram-positive and gram-negative bacteria. The was admitted for a reason other than that infection.[2] Nosocomial infections, findings will surely inform the development of new prophylactic treatments. which are facilitated primarily via urinary catheters, are a major cause of death and X. Han, G. Boix, M. Balcerzak, O. H. Moriones, M. Cano-Sarabia, increased morbidity among patients, causing 1 10 000 deaths N. Bastús, V. Puntes, I. Imaz, D. Maspoch every year in Europe.[3,4] Catalan Institute of Nanoscience and Nanotechnology (ICN2) Although bacterial and fungal infections can be treated with CSIC and The Barcelona Institute of Science and Technology antibiotics, increased and inappropriate use of antibiotics has Campus UAB, Bellaterra, Barcelona 08193, Spain E-mail: inhar.imaz@icn2.cat; daniel.maspoch@icn2.cat led to the emergence of highly menacing, multidrug-resistant M. Balcerzak bacteria. Accordingly, antimicrobial coatings of hospital sur- Institute of Materials Science and Engineering faces and medical equipment are garnering increasing interest Poznan University of Technology as a simple prophylactic strategy.[5] Such coatings impede the Jana Pawła II No 24, Poznan 61–138, Poland arrival and growth of microorganisms on surfaces, and main- O. H. Moriones tain their inhibitory or destructive activity against transitory Universitat Autònoma de Barcelona (UAB) Campus UAB, Bellaterra, Barcelona 08193, Spain microorganisms after each use, thereby lowering the pro­ P. Cortés, M. Llagostera bability of future infections resulting from surface-contact. Departament de Genètica i Microbiologia Typically, they are fabricated by incorporating biocides into Universitat Autònoma de Barcelona polymers or hydrogels, which are subsequently released in a Campus de Bellaterra, Cerdanyola del Vallès 08193, Spain controlled fashion. In many of the antimicrobial coatings used V. Puntes today, the biocide is silver nanoparticles (NPs),[6] silver salts,[7] Fundacio Hospital Universitari Vall D’Hebron – Institut De Recerca 08035, Passeig Vall D Hebron, Barcelona 119–129, Spain metal-oxide NPs,[8] antibiotics,[9] or quaternary ammonium V. Puntes, D. Maspoch compounds.[10] However, each of these current technologies ICREA suffers from certain limitations. For instance, silver-based coat- Pg. Lluıs Companys 23, Barcelona 08010, Spain ings, which are popular because they have been widely char- The ORCID identification number(s) for the author(s) of this article acterized and demonstrate impressive in vitro performance, can be found under https://doi.org/10.1002/adfm.202112902. actually exhibit low microbial efficacy under real conditions.[11] © 2022 The Authors. Advanced Functional Materials published by Finally, quaternary ammonium coatings have demonstrated Wiley-VCH GmbH. This is an open access article under the terms of to be efficient, acting by disrupting the cytoplasmic and outer the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original membrane lipid bilayers of bacteria; however, its performance work is properly cited, the use is non-commercial and no modifications can be reduced depending on the surface conditions (e.g., pH, or adaptations are made. presence of organic soil, hardness of water, and presence of The copyright line for this article was changed on 3 June 2022 after original blood).[11] online publication. Among the most efficient topical biocides is iodine, which DOI: 10.1002/adfm.202112902 is widely available, inexpensive, and has broad-spectrum Adv. Funct. Mater. 2022, 32, 2112902 2112902 (1 of 12) © 2022 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH 16163028, 2022, 19, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/adfm.202112902 by Spanish Cochrane National Provision (Ministerio de Sanidad), Wiley Online Library on [14/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License www.advancedsciencenews.com www.afm-journal.de antimicrobial activity.[12] Furthermore, it works by causing irre- 0.9 mgI2 mgcomposite–1), whereas the photoactive AuNR@SiO2 versible, nonspecific damage to microorganism cells; thus, unlike enables the active NIR-triggered release. Moreover, we demonstrate antibiotics, it does not lead to resistance.[13] However, the low that these AuNR@SiO2@UiO-66 microbead composites can be aqueous solubility of iodine limits its use in many applications. incorporated into organic polymers for developing iodine-based Moreover, although iodine is much more soluble in alcohols, antimicrobial films that retain the iodine adsorption capacity these solvents permeate tissue too rapidly, causing over-adminis- and both release mechanisms. We validated the antibacterial tration of the iodine, which in turn leads to irritation and other activity of our light-responsive films against gram-positive and undesirable side effects.[14] Since 1955, a water-based complex gram-negative bacteria. of polyvinylpyrrolidone (PVP) and iodine (also known as povi- done-iodine; sold as Betadine, Inadine, and Braunol) has been the dominant formulation of iodine for topical antimicrobial 2. Results and Discussion use. Iodine is also widely used in dental/prosthetic implants, in which it is electrochemically absorbed into titanium.[15] 2.1. Materials Synthesis and Characterization However, despite the many advantages of iodine, the aforemen- tioned challenges of solubility and release have precluded its AuNRs were prepared following a modified literature proce- use in antimicrobial films and coatings.[16] dure.[35] Thus, a gold seed solution was initially prepared fol- Reflecting on approaches to circumvent the limitations of lowing the traditional cetyltrimethylammonium bromide using iodine solutions directly in antimicrobial surface appli- (CTAB) stabilized synthesis.[35] The synthesized seeds were then cations, we envisioned that adsorption of iodine into porous placed into a growth solution with trace amounts of AgNO3, materials could enable both its storage and subsequent release, and left overnight to develop into AuNRs. The synthesized rods while preventing direct contact with human skin. Further- were washed with Mili-Q water upon centrifugation. Field-emis- more, we imagined that the resultant porous material could sion scanning electron microscopy (FE-SEM), transmission then be incorporated into polymeric matrices to yield antimi- electron microscopy (TEM) and UV-Vis spectroscopy revealed crobial films or coatings. Among the various types of porous the formation of AuNRs with dimensions (length × width) materials available to store iodine, we reasoned that metal- of ≈80 × 15 nm (aspect ratio, AR = 5) (Figure S1a,d, Supporting organic frameworks (MOFs) would be ideal. Indeed, MOFs Information), and with a maximum localized surface plasmon show high porosity, good thermal and chemical stability, and resonance (LSRP) peak at 810 nm (Figure S1e, Supporting tunable pore size, shape, and functionality, all of which would Information). The AuNRs were coated with a silica shell fol- facilitate selective adsorption and storage of iodine at loading lowing a modified Stöber process through a slightly adapted capacities higher than the mass of the host MOF. For instance, versions reported.[36–38] Briefly, a dispersion of synthesized the archetypical MOFs HKUST-1 and ZIF-8 have shown iodine AuNRs in a diluted CTAB solution (pH = 10) was reacted over- uptake capacities of 1.75 mg mg–1MOF and 1.25 mg mg–1MOF, night with tetraethyl orthosilicate (TEOS) in the presence of respectively.[17–19] Once adsorbed into MOFs, iodine can then 0.1 m of a sodium hydroxide solution as a catalyst in a metha- be released into solution.[20–22] Furthermore, many studies nolic solution. The resulting AuNRs coated with a silica shell have confirmed that MOFs can be efficiently incorporated into (AuNR@SiO2) of a thickness of 17 ± 2 nm (Figure S1b, Sup- organic polymer films to form mixed matrix-membranes, self- porting Information) were centrifuged, and then thoroughly folding films, and other types of functional films.[23–27] washed with ethanol. Finally, the silica shell thickness of Interestingly, MOFs can be designed to undergo triggered AuNR@SiO2 was increased by dispersing them in an ethanolic release of adsorbed species via stimuli such as pH or light.[28–30] solution of ammonia and TEOS under mild stirring. The final For example, a pH change that causes MOF degradation has AuNR@SiO2 had an Au content of 23% and a shell thickness of been used to release hosted drugs (e.g., doxorubicin and arte- 30 ± 3 nm, as confirmed by inductively coupled plasma-mass misinin) from the well-known MOFs ZIF-8 and MIL-100(Fe). spectrometry (ICP-MS), FE-SEM, and scanning transmission Alternatively, visible light has been used to provoke degrada- electron microcopy (STEM) (Figure 1a, Figure S1c, Supporting tion of a Zr-based MOF via isomerization of its azobenzen- Information). Importantly, this SiO2 coating was required to edicaboxylate linker, thereby liberating its cargo.[31] Photoactive prevent degradation of the AuNRs upon exposure to iodine: in nanomaterials such as polypyrrole[32] and metal NPs[33,34] have previous studies, we noticed that naked AuNRs encapsulated also been combined with MOFs to generate composites that in UiO-66 crystals were not stable to iodine at 75 °C, and that release their cargo upon exposure to visible or near-infrared they became etched even after only brief exposure (Figure S2a, (NIR) light. Supporting Information).[39] To this end, a coating thickness of Herein, we report the design, synthesis, and in vitro vali- around 30 nm of SiO2 was found to be optimal for protection dation of antibacterial activity of MOF-based composite films (Figure S2b, Supporting Information). that adsorb and store iodine at very high concentrations, and Next, we synthesized the AuNR@SiO2@UiO-66 composite can release it in two ways: slowly and passively at low con- microbeads following a spray-drying methodology previously centration; or, upon triggering by NIR light, rapidly and reported by our group (Figure 1a).[40] In a typical synthesis, a actively at high concentration. This composite is made of a dispersion of AuNR@SiO2 and the UiO-66 precursors (tere- spheri­cal microbead of the MOF UiO-66 that encapsulates gold phthalic acid and zirconium (IV) propoxide) dissolved in N,N- nanorods (AuNRs) coated with a silica shell (SiO2) (hereafter dimethylformamide (DMF) was injected into a coil-preheater, called AuNR@SiO2@UiO-66) (Figure 1a). The microporous and then spray-dried at 180 °C. The synthesis was repeated UiO-66 adsorbs and stores iodine (at concentrations of up to without AuNR@SiO2 to afford pristine UiO-66 microbeads. Adv. Funct. Mater. 2022, 32, 2112902 2112902 (2 of 12) © 2022 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH 16163028, 2022, 19, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/adfm.202112902 by Spanish Cochrane National Provision (Ministerio de Sanidad), Wiley Online Library on [14/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License www.advancedsciencenews.com www.afm-journal.de Figure 1. a) Schematic illustration of the spray-drying synthesis of AuNR@SiO2@UiO-66 microbeads, using AuNRs coated with a SiO2 shell (trans- mission electron microscopy, TEM image). b,c) Representative field-emission scanning electron microscopy (FE-SEM) (b) and high-angle annular dark-field scanning transmission electron microcopy (HAADF-STEM) (c) of AuNR@SiO2@UiO-66 microbeads. d) Powder X-ray diffraction (PXRD) for simulated UiO-66 (blue), AuNR@SiO2 (green), UiO-66 microbeads (black), and AuNR@SiO2@UiO-66 microbeads (red). Scale bars: 100 nm (a), 20 µm (b), and 1 µm (c). Powder X-ray diffraction (PXRD) and FE-SEM revealed the for- with NIR light (λ = 810 nm) at increasing intensity (52, 224, mation of spherical microbeads of both UiO-66 and AuNR@ and 1000 mW cm–2) and the temperature was monitored using SiO2@UiO-66 (Figure 1b,d). Moreover, the successful encap- a thermal camera (Table S1, Supporting Information). The pris- sulation of AuNR@SiO2 in UiO-66 microbeads was confirmed tine UiO-66 microbeads did not respond photothermally to the by high-angle annular dark-field (HAADF-STEM) imaging NIR light; their temperature remained constant throughout (Figure 1c). The content of Au in the composite microbeads the irradiation. Contrariwise, the AuNR@SiO2@UiO-66 micro- was estimated by first digesting them in an 8:3 mixture of 70% beads heated up rapidly (in less than 60 s; Figure S4, Supporting HNO3 and HF at 230 °C, and then analyzing the byproducts by Information): at an intensity of 52 mW cm–2, up to 90 °C; at ICP-MS, from which an AuNR@SiO2 content of 9% was deter- 224 mW cm–2, up to 150 °C; and finally, at 1000 mW cm–2, up mined. Nitrogen isotherm adsorption measurements revealed to 274 °C. Remarkably, they also cooled down just as quickly, BET surface areas of 1040 m2 g–1 for the UiO-66 microbeads as demonstrated once the NIR light had been turned off. This and 750 m2 g–1 for the AuNR@SiO2@UiO-66 microbeads property of equivalently rapid heating and cooling is critical for (Figure S3, Supporting Information). Note that this latter value precise switching (on/off) of triggered release. is close to the expected value (946 m2 g–1), as calculated based on the loading percentage of AuNR@SiO2 within the AuNR@ SiO2@UiO-66 microbeads. 2.2. Adsorption and NIR-Light Triggered Release of Iodine Once we had synthesized the AuNR@SiO2@UiO-66 microbeads, we studied their photothermal proper- We then determined the iodine-uptake capacity of the pristine ties to ascertain their potential utility as a photoactivat- UiO-66 microbeads and the composite AuNR@SiO2@UiO-66, able system for release of iodine. To this end, UiO-66 and using a solid–gas adsorption setup. The sublimation chamber AuNR@SiO2@UiO-66 microbeads were separately irradiated comprised two glass tubes of known mass, sealed at one end, Adv. Funct. Mater. 2022, 32, 2112902 2112902 (3 of 12) © 2022 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH 16163028, 2022, 19, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/adfm.202112902 by Spanish Cochrane National Provision (Ministerio de Sanidad), Wiley Online Library on [14/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License www.advancedsciencenews.com www.afm-journal.de Figure 2. a) Iodine-adsorption isotherm at 75 °C for both UiO-66 (black) and AuNR@SiO2@UiO-66 (red) microbeads. b–d) Iodine-release profiles for UiO-66 (black) and AuNR@SiO2@UiO-66 (red) microbeads as triggered by near-infrared light (NIR) light at intensities of 1000 mW cm–2 (b), 224 mW cm–2 (c), and 52 mW cm–2 (d). and placed inside a scintillation vial, into which the microbeads the composite of I2@UiO-66 microbeads with encapsulated and the elemental iodine were separately introduced. Next, AuNR@SiO2 showed greater iodine-release than did the the sublimation chamber was purged with Ar gas to evacuate I2@UiO-66 (Figure 2b–d) microbeads alone. Thus, for I2@ any humidity that could induce errors in gravimetric meas- AuNR@SiO2@UiO-66, the iodine-release values were 28% urements, and the vial was placed inside an oven preheated to (0.26 mgI2 mgcomposite–1) at 52 mW cm−2 irradiation; 48% 75 °C. The optimum loading time was determined by periodi- (0.44 mgI2 mgcomposite–1) at 224 mW cm−2; and 74% (0.67 mgI2 cally removing a sample of UiO-66 microbeads from the oven mgcomposite–1) at 1000 mW cm−2. In contrast, for I2@UiO-66, the at different time intervals and carefully weighing the glass tube values were 8% (0.09 mgI2 mgcomposite−1) at 52 mW cm−2 irra- containing it. This experiment was also repeated with a sample diation; 16% (0.18 mgI2 mgcomposite−1) at 224 mW cm−2 irradia- of AuNR@SiO2@UiO-66 microbeads. The resulting isothermal tion; and 45% (0.49 mgI2 mgcomposite−1) at 1000 mW cm−2 irra- curves revealed a linear adsorption of iodine for the first 10 h, diation. Note that, although I2@UiO-66 released much less followed by saturation and finally, plateau of the adsorption iodine than what I2@AuNR@SiO2@UiO-66 did upon NIR after 20 h (Figure 2a). The exact uptake of iodine was confirmed irradiation, it did release more iodine than expected, given the by gravimetric experiments of samples after 20 h of adsorption, negligible photothermal properties of pristine UiO-66. This can revealing a maximum uptake of 1.1 mgI2 mgcomposite–1 for the be attributed to the intrinsic photothermal properties of iodine, pristine UiO-66 microbeads, and of 0.9 mgI2 mgcomposite–1 for which led to I2@UiO-66 being heated up to 44 °C, when irradi- the composite AuNR@SiO2@UiO-66 microbeads (Figure S5, ated at 52 mW cm–2; 90 °C, at 224 mW cm–2; and 120 °C, at Supporting Information). PXRD and HAADF-STEM imaging 1000 mW cm–2. For comparison, iodine-release from the cor- of UiO-66 microbeads and AuNR@SiO2@UiO-66 microbeads responding samples without NIR irradiation was also recorded. loaded with iodine did not reveal any signs of material degrada- Without irradiation, the iodine-loss for I2@AuNR@SiO2@ tion (Figure S6, Supporting Information). UiO-66 microbeads was 3% (0.025 mgI2 mgcomposite−1) and Next, we studied the NIR light-triggered release of iodine for the I2@UiO-66 microbeads, 4% (0.034 mgI2 mgcomposite−1) using a custom setup inside a thermogravimetric analyzer. (Figure S7, Supporting Information). To this end, I2@UiO-66 and I2@AuNR@SiO2@UiO-66 microbeads were placed inside the unit, allowed to stand undisturbed for 5 min to stabilize their weight, and finally, 2.3. Integration of Au@SiO2@UiO-66 Microbeads into PVDF Films irradiated (at 52, 224, and 1000 mW cm−2) for 35 min. During irradiation, the weight of the microbeads was recorded to Having confirmed the NIR-triggered release of iodine from detect the loss of iodine. As expected, upon NIR irradiation, our I2@AuNR@SiO2@UiO-66 microbeads, we then sought Adv. Funct. Mater. 2022, 32, 2112902 2112902 (4 of 12) © 2022 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH 16163028, 2022, 19, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/adfm.202112902 by Spanish Cochrane National Provision (Ministerio de Sanidad), Wiley Online Library on [14/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License www.advancedsciencenews.com www.afm-journal.de Figure 3. a-c) Field-emission scanning electron microscopy (FE-SEM) of the cross-section of the films containing AuNR@SiO2@UiO-66 microbeads at 25% (w/w). In (c), the microbeads are highlighted in pale green to better illustrate encapsulation of them. d,e) FE-SEM of the cross-section of the films containing AuNR@SiO2@UiO-66 microbeads at 8% (d) or 46% (e) (w/w). f) Powder X-ray diffraction (PXRD) of a pristine polyvinylidene difluoride (PVDF) film (black), AuNR@SiO2@UiO-66 microbeads (purple), and films containing AuNR@SiO2@UiO-66 microbeads at 8% (red), 25% (blue) or 46% (green) (w/w). Scale bars: 200 µm (a), 50 µm (b), 5 µm (c), 50 µm (d), and 50 µm (e). to integrate them into a polymeric film, with the ultimate aim AuNR@SiO2@UiO-66 microbeads retained their morphology of fabricating a coating for antibacterial applications in which and were homogeneously dispersed throughout (Figure 3b–e, sterilization could be selectively triggered. To this end, AuNR@ Figure S8, Supporting Information). Moreover, PXRD analysis SiO2@UiO-66 microbeads were encapsulated into a polyvi- of the three films containing the microbeads revealed that their nylidene difluoride (PVDF) film using a previously reported crystalline structure had not been affected during film forma- procedure.[25] In a typical synthesis, the necessary amount tion (Figure 3f). Quantification of the exact mass percentage of AuNR@SiO2@UiO-66 microbeads [10%, 30% and 50% (w/w)] AuNR@SiO2@UiO-66 microbeads inside the films by ICP-MS were dispersed in a PVDF solution in DMF and drop-cast analysis revealed values of 8%, 25%, and 46% (w/w) for the onto a glass surface. The DMF was evaporated off by placing films fabricated with 10%, 30%, and 50% (w/w) of microbeads, the glass slide in an oven (140 °C) for 30 min. The fabricated respectively. films were then thoroughly washed with methanol and finally, To evaluate the iodine-uptake capacity of the three composite dried under vacuum overnight. For comparison, a PVDF film films (Figure 4a), we started by measuring the capacity of a sec- without AuNR@SiO2@UiO-66 microbeads also was prepared tion (2 cm2) of the bare film (i.e., film lacking microbeads) to by the method. FE-SEM imaging of the cross-section of each adsorb iodine using the same procedure as we described for film revealed a thickness of 140 µm (Figure 3a), in which the the AuNR@SiO2@UiO-66 microbeads, in which we quantified Adv. Funct. Mater. 2022, 32, 2112902 2112902 (5 of 12) © 2022 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH 16163028, 2022, 19, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/adfm.202112902 by Spanish Cochrane National Provision (Ministerio de Sanidad), Wiley Online Library on [14/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License www.advancedsciencenews.com www.afm-journal.de the iodine-loading by thermogravimetric analysis (Figure S9, Supporting Information). The bare film barely adsorbed iodine (5 × 10–4 mgI2 mgfilm–1). Contrariwise, for similar experiments performed on sections (2 cm2) of films loaded with microbeads, the following sorption capacities were observed, according to the maximum possible iodine adsorption of the AuNR@SiO2@ UiO-66 microbeads within each film: at 8% microbead-loading, 0.012 mgI2 mgfilm–1 (17% of expected value [0.072 mgI2 mgfilm–1]); at 25% loading, 0.159 mgI2 mgfilm–1 (71% of the expected value [0.225 mgI2 mgfilm–1]); and at 46% loading, 0.434 mgI2 mgfilm–1 (105% of the expected value [0.414 mgI2 mgfilm–1) (Figure 4b). These results confirm that AuNR@SiO2@UiO-66 microbeads can adsorb iodine even when encapsulated into PVDF films and illustrate that the adsorption increases with increasing microbead loading. We attributed this behavior to the fact that, as the microbeads content increases, so does the number of interfacial voids formed between the polymer and composite beads, and consequently, so does the permeability. Interestingly, this phenomenon has already been described in MOF-based mixed-matrix membranes, in which the formation of interfacial voids arising from poor adhesion of the polymer matrix and porous filler particles are typically observed.[31] Moreover, micro- bead loading negatively correlates to the temperature required to fully desorb the iodine from the films: at 8% microbead- loading, that temperature is 240 °C; at 25%, 220 °C; and at 46%, 200 °C (Figure S9, Supporting Information). In fact, the final value is very close to that observed for the bare AuNR@SiO2@ UiO-66 microbeads (190 °C), again corroborating a higher number of interfacial voids or greater hierarchical porosity in the composite films. We then studied the triggered release of iodine from the three composite films by the same methodology that we pre- viously used for I2@AuNR@SiO2@UiO-66 microbeads. To this end, the films containing microbeads at different load- ings were independently placed inside the thermogravimetric analysis ((TGA) setup, allowed to stand undisturbed for 10 min to stabilize their weight, and finally, irradiated at 52 or 224 mW cm–2 for 35 min, while iodine loss was recorded. Upon irradiation, the following values for maximum release of total loaded iodine were recorded: at 8% microbead-loading, 17% (0.002 mgI2 mgfilm–1); at 25% microbead-loading, 18% (0.029 mgI2 mgfilm–1); and at 46% microbead-loading, 17% (0.073 mgI2 mgfilm–1) (Figure 4d). Alternatively, upon irra- diation at 224 mW cm–2, the corresponding recorded values were: at 8% microbead-loading, 28% (0.004 mgI2 mgfilm–1); at 27% microbead-loading, 18% (0.044 mgI2 mgfilm–1); and at 46% microbead-loading, 30% (0.121 mgI2 mgfilm–1) (Figure 4c). In all these composite films, these results obtained represent nearly 63% of the expected release according to their contents of AuNR@SiO2@UiO-66 microbeads. We rationalized the fact that less iodine was released from the composite films than from the pure AuNR@SiO2@UiO-66 microbeads under the of iodine at 75 °C for the films containing AuNR@SiO2@UiO-66 micro- beads at 8% (red), 25% (blue), or 46% (green) (w/w). c,d) Light-trig- Figure 4. a) Photographs of the composite films containing different con- gered iodine- release profiles for the films containing I2@AuNR@SiO2@ centrations of AuNR@SiO2@UiO-66 microbeads before (top) and after UiO-66 microbeads at 8% (red), 25% (blue), or 46% (green) (w/w) under (bottom) loading with iodine. Scale bar: 2 cm. b) Adsorption isotherm irradiation intensities of 224 mW cm–2 (c) and 52 mW cm–2 (d). Adv. Funct. Mater. 2022, 32, 2112902 2112902 (6 of 12) © 2022 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH 16163028, 2022, 19, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/adfm.202112902 by Spanish Cochrane National Provision (Ministerio de Sanidad), Wiley Online Library on [14/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License www.advancedsciencenews.com www.afm-journal.de release via repetitive cycles of on/off switching. To this end, two portions of film containing 25% I2@AuNR@SiO2@UiO-66 microbeads were irradiated at 52 or 224 mW cm–2 for 1 min, after which the light was turned off for 3 min. This on/off cycle was ultimately repeated 50 times. At both intensities, the films demonstrated stepwise release of iodine via on/off switching (Figure 5a and Figure S11a, Supporting Information): turning the NIR light on released the iodine, but turning it off slowed the release down. The iodine release occurred in a burst in the first switching cycle (0.006 mgI2 mgfilm–1 at 52 mW cm–2; and 0.016 and at 224 mW cm–2), decreased until reaching a plateau at the fifteenth cycle, and then stayed constant for the remaining cycles (9 × 10–5–8 × 10–5 mgI2 mgfilm–1 at 52 mW cm–2; and 1.7 × 10–4–1,6 × 10–4 mgI2 mgfilm–1 at 224 mW cm–2) (Figure 5b and Figure S11b, Supporting Information). 2.3.1. Antibacterial Activity Having demonstrated the controlled release of iodine from the UiO-66 and AuNR@SiO2@UiO-66 microbeads and composite films, we next ascertained their antibacterial activity, begin- ning with the disk-diffusion method. The UiO-66 microbeads and the AuNR@SiO2@UiO-66 microbeads lacking iodine did not impair the growth of Escherichia coli (gram-negative bacte- rium) or Staphylococcus aureus (gram-positive bacterium), even under irradiation with NIR light. Contrariwise, UiO-66 micro- beads and AuNR@SiO2@UiO-66 microbeads loaded with iodine each led to well-defined inhibition growth zones, both with and without NIR irradiation. The diameters of the respec- tive growth-inhibition zones were higher against S. aureus (31 to 33 mm) than against E. coli (24 to 26 mm). Interestingly, there were no significant differences between loaded I2@UiO-66 or I2@AuNR@SiO2@UiO-66 products (Figure S12, Supporting Figure 5. a) Stepwise release of iodine from a composite film containing Information). Notably, the growth-inhibition obtained with I2@AuNR@SiO2@UiO-66 microbeads at 25% (w/w) irradiated with both types of materials were higher than that produced by near-infrared light (NIR) light at 52 mW cm–2 and subjected to on/off povidone-iodine (common antiseptic with a broad spectrum switching. b) Zoom on the stepwise release after its stabilization at the 15th cycle. of antimicrobial activity) at similar concentrations of iodine, for which the growth-inhibition zones had diameter against S. aureus was 10 mm and against E. coli, 7 mm (data not shown). same conditions according to the diffusion barrier generated Additionally, the composite films prepared at different iodine- by the polymeric films. Finally, and as in the earlier iodine-loss containing microbead-loadings (8%, 25%, or 46%) and tested experiments, the iodine-loss in the absence of irradiation was on E. coli cultures also produced inhibition zones, the diam- recorded for comparison, for which the recorded values were: eters of positively correlated significantly (p < 0.0001) to iodine at 8% microbead-loading, 3.1% (4 × 10–4 mgI2 mgfilm–1); at 25% concentration (Figure S13 and Table S2, Supporting Informa- microbead-loading, 3.3% (0.006 mgI2 mgfilm–1); and at 46% tion). These results demonstrated the capacity of iodine to be microbead-loading, 4.1% (0.014 mgI2 mgfilm–1). persistently released from UiO-66 or AuNR@SiO2@UiO-66 Finally, without irradiation, the films containing microbeads microbeads, either in the solid-state or when incorporated in at 25% or 46% (w/w) exhibited slow and prolonged release films, throughout the agar layer during overnight incubation at (Figure S10, Supporting Information), liberating ≈50% of their 37 °C. However, NIR irradiation did not enhance the antibac- total iodine content over 2 months. This release was faster in terial activity of the iodine-loaded I2@AuNR@SiO2@UiO-66 the first month, after which the film at 25% microbead-loading composites. We partially expected this behavior as, in these released, on average, 2 × 10–4 mgI2 mgfilm–1 iodine per day, and experiments, we only evaluated the antibacterial activity of iodine the film at 46% microbead-loading, 4 × 10–4 mgI2 mgfilm–1 per release through diffusion along the agar inoculated with bacterial day. suspensions: we did not assess the activity of the iodine released Once we had demonstrated that, even when I2@AuNR@ through the air passively or actively (i.e., via light-triggering). SiO2@UiO-66 microbeads were incorporated into polymer To solve the aforementioned problem, and to evaluate the films, they could still trigger the release of iodine upon NIR antibacterial performance of the composite films upon iodine irradiation, we then explored the possibility of controlling this release through the air by sublimation via both the passive and Adv. Funct. Mater. 2022, 32, 2112902 2112902 (7 of 12) © 2022 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH 16163028, 2022, 19, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/adfm.202112902 by Spanish Cochrane National Provision (Ministerio de Sanidad), Wiley Online Library on [14/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License www.advancedsciencenews.com www.afm-journal.de Figure 6. a–c) Schematic illustrations of the three experiments performed to study the passive (a) or light-triggered (b,c) antibacterial performance of the composite films containing iodine-loaded I2@AuNR@SiO2@UiO-66 microbeads. d–i) Corresponding inhibition growth zones of Escherichia coli cultures produced in composite films containing microbeads at 8% (d–f) or 25% (g–i) (w/w). Left (d,g): photographs taken after co-incubation of both composite film and agar plate inoculated with E. coli. Center (e,h) and right (f,i): photographs taken after incubation of the agar plate inoculated with E. coli once the composite films had been removed. The composite films shown in (f,i) had been irradiated with near-infrared light (NIR) light. Ø: diameter of the growth-inhibition zone. Values are the average of at least four replicates ± standard deviation. the light-triggered mechanisms, we designed a new experi- In the above three experiments, we observed that passive mental setup and performed multiple experiments with it. It release of iodine via sublimation inhibited the growth of both comprised placing a 1 cm2 portion of each composite film, con- E. coli (Figure 6d,g) and S. aureus (Figure 7a,d). Moreover, we taining iodine-loaded I2@AuNR@SiO2@UiO-66 microbeads at also observed that the light-triggered release of iodine inhibited either 8% or 25%, over a plate cover, and then putting the agar the growth of both bacteria (Figure 6e,f,h,i, and Figure 7b,c,e,f). plate inoculated with bacterial suspensions face down on the In all cases, the inhibition zones had a larger diameter in the cover, such that the distance between the film and agar plate irradiated experiments than in the nonirradiated ones. In E. coli was fixed to 1.6 cm. Next, three different experiments were per- cultures, these differences were statistically significant when formed. In the first experiment, the two plates were co-incubated the films containing 8% (p = 0.0002) and 25% microbeads at 37 °C for 18 h to evaluate the antibacterial performance con- (p < 0.0001) were irradiated and nonirradiated for 5 min and ferred by passive iodine release (Figure 6a). In the second, then removed. Regarding S. aureus, statistically results were the composite film was irradiated with NIR light (intensity: obtained at 25% (p < 0.0001) (Tables S3 and S4, Supporting 224 mW cm–2) for 5 min. Then, the composite film was imme- Information). This is in quite contrast to identical experiments diately removed, and the agar plate was sealed with parafilm performed with films that do not contain AuNR@SiO2 NPs, in and finally, incubated at 37 °C for 18 h (Figure 6c). The third which the inhibition zones were similar in the irradiated and experiment was similar to the second one, except that the film nonirradiated experiments (Figure S14, Supporting Informa- was not irradiated (Figure 6b). These last two experiments were tion). Importantly, the antibacterial activity of the irradiated designed to enable evaluation of the antibacterial performance composite films also positively correlated with the content of conferred by the light-triggered release of iodine. In all cases, iodine-loaded I2@AuNR@SiO2@UiO-66 microbeads. The film the corresponding control conditions using composite films containing microbeads at 8% (w/w) exhibited greater antibacte- without iodine and/or without irradiation also were tested. rial activity against S. aureus than against E. coli; however, this Adv. Funct. Mater. 2022, 32, 2112902 2112902 (8 of 12) © 2022 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH 16163028, 2022, 19, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/adfm.202112902 by Spanish Cochrane National Provision (Ministerio de Sanidad), Wiley Online Library on [14/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License www.advancedsciencenews.com www.afm-journal.de Figure 7. Growth-inhibition zones in Staphylococcus aureus cultures generated by composite films containing iodine-loaded I2@AuNR@SiO2@UiO-66 microbeads at 8% (a–c) or 25% (d–f) (w/w). Left (a,d): photographs taken after co-incubation of the composite film and an agar plate inoculated with S. aureus. Center (b,e) and right (c,f): photographs taken after incubation of an agar plate inoculated with S. aureus, after the composite films had been removed. The composite films shown in (c,f) had been irradiated with near-infrared light (NIR) light. Ø: diameter of the growth-inhibition zone. Values are the average of at least four replicates ± standard deviation. difference was less pronounced for the film containing micro- AuNR@SiO2@UiO-66 microbeads could be incorporated beads at 25% (w/w). Altogether, these results confirmed the at different concentrations into organic polymers to afford effective passive, long-lasting antibacterial activity of our com- iodine-based antibacterial films that retain the iodine adsorp- posite films against gram-positive and gram-negative bacteria tion capacity, and dual release mechanisms, of the parent and that this activity can be enhanced by irradiating the films composite. Finally, the passive and light-triggered antibacterial with NIR light to trigger release of iodine. performance of these composite films was confirmed against S. aureus (gram-positive) and E. coli (gram-negative), opening the way to develop new smart prophylactic coatings. We are 3. Conclusions confident that these encouraging findings on our iodine-loaded I2@AuNR@SiO2@UiO-66 composite and related thin films We designed, synthesized, and validated for antibacterial will inform future efforts at developing new iodine-based anti- activity in vitro, a MOF composite that can store iodine and bacterial materials designed to prevent nosocomial and other then, release it two ways: either passively and slowly, or, upon microbial infections, including coatings for medical instru- triggering by NIR light, actively and quickly. The composite ments or hospital surfaces. comprises SiO2-coated AuNRs encapsulated within micro- beads of the MOF UiO-66, which is then loaded with iodine and can be produced as thin films. The AuNR@SiO2@UiO-66 4. Experimental Section composite was synthesized by a scalable, continuous-flow, spray-drying methodology, enabling facile and homogeneous Materials and Methods: Zirconium (IV) propoxide solution distribution of the encapsulated photoactive AuNR@SiO2 NPs (70% (w/w)) in 1-propanol, terephthalic acid, gold(III) chloride hydrate, TEOS ≥ 99.0%, glacial acetic acid, sodium hydroxide, throughout the microbeads. We found that the silica coating cetyltrimethylammonium bromide, sodium borohydride, silver nitrate, around the AuNRs was essential to synthesize a long-life com- ascorbic acid, absolute ethanol ≥ 99.8%, and ammonium hydroxide posite, as bare AuNRs were degraded upon exposure to iodine. 28% were purchased from Sigma Aldrich. N,N- DMF, methanol, ethanol, The microporous UiO-66 can adsorb and store iodine at con- sulfuric acid, and acetone were purchased from Fisher Scientific. All centrations of up to 0.9 mgI2 mgcomposite–1, and then release it the reagents were used without further purification. Deionized water, either passively over time, or actively, upon irradiation with obtained with a Milli-Q system (18.2 MΩ cm), was used when required. PXRD patterns were collected on an X’Pert PRO MPDP analytical NIR light, which heats the composite to temperatures of up to diffractometer (Panalytical) at 45 kV and 40 mA using CuKα radiation 274 °C. Intriguingly, rapid heating and cooling of the AuNR@ (λ = 1.5419 Å). Nitrogen adsorption and desorption measurements were SiO2@UiO-66 composite enabled stepwise release of iodine collected at 77 K using an ASAP 2460 (Micromeritics). Temperature for through selective on/off switching. Next, we showed that these N2 isotherms measurement was controlled by using a liquid nitrogen Adv. Funct. Mater. 2022, 32, 2112902 2112902 (9 of 12) © 2022 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH 16163028, 2022, 19, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/adfm.202112902 by Spanish Cochrane National Provision (Ministerio de Sanidad), Wiley Online Library on [14/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License www.advancedsciencenews.com www.afm-journal.de bath. FE-SEM images were collected on a Magellan 400 L scanning UiO-66 microbeads, the above procedure was repeated without the electron microscope (FEI) at an acceleration voltage of 5.0 KV. TEM addition of the AuNR@SiO2 particles. images were collected on a Tecnai G2 F20 microscope (FEI) at 200 KV. Fabrication of Films Containing AuNR@SiO2@UiO-66 Microbeads: ICP-MS experiments were performed on an Agilent 7500. Laser All the films were prepared following a with slightly modified version irradiation was performed using a Lasiris Powerline 810 (Coherent). of a previously reported procedure.[25] To fabricate the films containing Thermal imaging was obtained using a PI 450 (Optris) infrared camera. AuNR@SiO2@UiO-66 microbeads at 8%, 25% or 46% (w/w), 25, 75, or Inductively Coupled Plasma–Optical Emission Spectroscopy (ICP-MS) 125 mg of the microbeads, respectively, were thoroughly dispersed into measurements were performed on an Agilent 7500. TGA experiments 0.125, 0.375, or 0.625 mL of DMF, respectively, and then sonicated for were run on a Perkin-Elmer-TGA-8000G, under N2 atmosphere. 15 min. Simultaneously, 225, 175, or 125 mg of PVDF, respectively, were Synthesis of AuNRs: The AuNRs were synthesized through a seed- dissolved in 1.125, 0.875, or 0.625 mL of DMF, respectively, by heating mediated growth procedure adapted from the literature.[35] In a typical at 60 °C. For each microbead-loading level, the two solutions were synthesis, 273.4 mg of CTAB was dissolved in 7.5 mL H2O inside a mixed, and then stirred for 20 min, and then the resulting mixture was 15 mL scintillation vial under magnetic stirring. Next, 2 mL of a HAuCl4 drop-casted onto a glass surface, and placed inside an oven preheated (24 × 10−3 m) solution was added, and the resultant mixture was stirred to 140 °C for 30 min. The resulting films were detached from the glass for 10 s. Afterwards, 0.6 mL of ice-cold aq. NaBH4 (10 × 10−3 m) was slide by submerging them in water, and then placed inside an autoclave added, and the mixture was stirred at 600 rpm for 2 min. Finally, the filled with methanol. After solvent exchange at 85 °C overnight inside the magnetic stir-bar was removed, and the seed solution was allowed to autoclave, the resultant clean films were recovered, and then dried under react for 3 h at 28 °C. In parallel, 437.4 mg CTAB was dissolved in 10 mL dynamic vacuum at 85 °C. of H2O inside a 20 mL scintillation vial under magnetic stirring. Then, Photothermal Activity: The photothermal activity of the synthesized sequentially, 204 µL of aq. HAuCl4 (24 × 10−3 m), 0.2 mL of aq. H2SO4 microbeads was confirmed with a thermal camera by irradiating them (0.5 m), 75 µL of aq. AgNO3 (0.01 m), and 80 µL of aq. ascorbic acid at 52, 224, or 1000 mW cm–2, which corresponded to a distance between (0.1 m) were added into the solution, with 10 s of stirring between each the laser and microbeads of 15, 7, or 2 cm, respectively. addition. Next, 24 µL of the above-prepared seed solution was added Iodine Uptake: The iodine-adsorption studies were done by combining into this solution, and the resultant mixture was vigorously stirred for either 6 mg of microbeads or a 2-cm2 portion of film, and 10 mg of 30 s. The magnetic stir-bar was removed, and the mixture was left to elemental iodine, into two different glass tubes (previously tared) react at 28 °C for 12 h. Finally, the resulting AuNRs were separated with one end sealed. Then, the two containers were introduced into a through centrifugation, and then washed twice in Milli-Q water to scintillation vial purged with Ar to remove any moisture that could remove any excess CTAB. interfere with gravimetric measurements. The vial was then heated to Coating of AuNRs with a Silica Shell: The AuNRs were coated with 75 °C inside an oven for 20 h. At different periods of time, a small aliquot a silica shell following a slightly modified combination of reported of microbeads, or a small piece of the film, were collected from the vial, procedures.[36–38] Thus, the synthesized AuNRs were dispersed in 10 mL and the uptake of iodine in each sample was determined by TGA. of aqueous 0.6 × 10−3 m CTAB solution, and the resulting mixture was Light-Triggered Release of Iodine: In a typical experiment, either stirred for 12 h. The pH of the AuNR dispersion was then adjusted 0.3 mg of microbeads or a small piece (≈1 mg) of film loaded with to 10.0 to 10.4 using aq. NaOH solution (0.1 m), and the mixture was iodine were placed inside a TGA pan, which was then loaded into the stirred for 30 min. Afterwards, 90 µL of freshly prepared 20% (v/v) TEOS TGA analyzer preset to 30 °C. The samples were then left for 10 min to in methanol was added, and the resulting solution was stirred gently at enable stable measurements. Afterwards, the samples were irradiated 70 rpm for a further 30 min. Finally, the magnetic stir-bar was removed, for 35 min under NIR light at intensities of 52, 224, or 1000 mW cm–2, and the reaction mixture was left at 28 °C overnight. The obtained silica- and loss in weight of each sample was recorded. The recorded weight coated rods (hereafter named AuNR@SiO2) were washed three times by loss was compared with the total amount loaded and the release centrifugation and redispersion in ethanol. The thickness of the silica- percentage calculated. The experiments were repeated three times for shell coating was confirmed by FE-SEM/TEM imaging to be 17 ± 2 nm. each sample. The silica coating was thickened following a modified Stöber process.[36] Stepwise Light-Triggered Release of Iodine by on/off Switching: The on/ First, the AuNR@SiO2 were concentrated into 2 mL of absolute ethanol off switching experiment began with a small piece (≈1 mg) of an iodine- and then, they were redispersed under mild sonication. Later, AuNR@ loaded film being placed inside a TGA pan, which was then loaded into SiO2 were placed into a 40 mL of absolute ethanol that contained 1.2 mL a TGA analyzer preset to 30 °C. The sample was then left for 10 min of ammonia NH4OH (28%) and 200 µL of a TEOS solution prepared to enable stable measurements. Next, the film was irradiated for 1 min in ethanol with a final concentration of 100 × 10−3 m. The mixture was under NIR light at intensities 52 or of 224 mW cm–2, after which point left under mild stirring overnight. The final thickness of the silica-shell the laser was turned off for 3 min. The weight loss of the sample was coating was 30 ± 3 nm. Finally, the obtained AuNR@SiO2 were washed continuously recorded throughout the process. This on/off cycle was to eliminate unreacted products, three times with methanol and three repeated 50 times. times with DMF, redispersed in 2 mL DMF, and finally, stored in a Antibacterial Activity Assays: The antibacterial activity of UiO-66 refrigerator until used. microbeads, AuNR@SiO2@UiO-66 microbeads, and their corresponding Synthesis of AuNR@SiO2@UiO-66 Composite Microbeads: The composite films was assessed in different experiments. This began with AuNR@SiO2@UiO-66 microbeads were synthesized using a slightly a disk-diffusion experiment, in which cultures of E. coli (ATCC 25922) modified version of a previously reported spray-drying method.[40] Briefly, and S. aureus (ATCC 25923) were prepared in Luria–Bertani (LB) agar terephthalic acid (1 mmol, 166 mg), glacial acetic acid (4 mL), the plates, and then incubated at 37 °C for 18 h. Next, bacterial suspensions dispersion of AuNR@SiO2 particles in DMF (2 mL), and a 70% (w/w) were prepared with PBS 1× and adjusted at DO550 nm = 0.2 (equivalent solution of zirconium (IV) propoxide (Zr(OPrn)4) in 1-propanol (1 mmol, to 108 CFU mL−1). The bacterial suspensions were smeared on the LB 309 µL) were sequentially added to a flask containing 10 mL of DMF. The plates using cotton swabs that had been dipped in the suspensions. resulting mixture was injected into a coil-flow reactor (inner diameter: Whatman disks (diameter: 6 mm) were aseptically deposited onto the 3 mm) at a feed rate of 2.4 mL min–1 at 115 °C. The resulting preheated LB agar surface, and UiO-66 microbeads or AuNR@SiO2@UiO-66 solution was then spray-dried at 180 °C (flow rate: 336 mL min–1), microbeads (≈1–1.6 mg), with or without iodine, were placed over the using a B-290 Mini Spray-Dryer (BÜCHI Labortechnik; spray cap hole disks. In the case of the composite films containing AuNR@SiO2@ diameter: 0.5 mm). The resulting AuNR@SiO2@UiO-66 microbeads UiO-66 microbeads at 8%, 25%, or 46% (w/w), with or without iodine, were dispersed in DMF, washed twice with DMF and ethanol, and were directly placed on the LB agar surface. Some of these samples were finally, dried for 12 h at 85 °C under dynamic vacuum overnight. The irradiated for 5 min under NIR light at an intensity of 224 mW cm–2. The percentage of AuNR@SiO2 NPs encapsulated within the microbeads plates were left for at 4 °C for 1 h, and then incubated at 37 °C for 18 h. was determined by ICP-MS to be 9% (w/w). To synthesize the pristine Each experiment was done in duplicate. Adv. Funct. Mater. 2022, 32, 2112902 2112902 (10 of 12) © 2022 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH 16163028, 2022, 19, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/adfm.202112902 by Spanish Cochrane National Provision (Ministerio de Sanidad), Wiley Online Library on [14/10/2022]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License www.advancedsciencenews.com www.afm-journal.de Next, the antibacterial performance of the composite films upon [1] COVID Live Update: 174,753,370 Cases and 3,762,987 Deaths from iodine release through the air via sublimation provoked by the passive the Coronavirus – Worldometer, https://www.worldometers.info/ or by the active (light-triggered) iodine-release mechanism was coronavirus/ (accessed: June 2021). ascertained. To this end, each composite film (size: 1 cm2) containing [2] H. A. Khan, F. K. Baig, R. Mehboob, Asian Pac. J. Trop. Biomed. 2017, either 8% or 25% (w/w) AuNR@SiO2@UiO-66 microbeads loaded 7, 478. with iodine was positioned over a plate cover, and then an agar plate [3] E. Bouza, S. Alonso, A. Asensio, G. De Juan, C. G. Lucio, C. Larrosa, inoculated with a bacterial suspension was placed face down on it. The J. López-Iglesias, P. Muñoz, R. Sierra, J. Perianes, J. L. De la Serna, distance between the composite film and the agar plates was fixed to E. Palomo, D. Gracia, Rev. Esp. Quimioter. 2019, 32, 165. 1.6 cm. Then, three different experiments were performed. In the first [4] V. Iacovelli, G. Gaziev, L. Topazio, P. Bove, G. Vespasiani, E. F. Agrò, one, the two plates were incubated together at 37 °C for 18 h (Figure 6a). Urologia 2014, 81, 222. In the second experiment, the composite film was irradiated with NIR [5] M. Cloutier, D. Mantovani, F. Rosei, Trends Biotechnol. 2015, 33, light (224 mW cm–2) for 5 min, during which time the plates were 637. rotated. Next, the composite film was immediately removed, and the culture agar plate was sealed with parafilm and incubated at 37 °C for [6] I. I. Niyonshuti, V. R. Krishnamurthi, D. Okyere, L. Song, 18 h (Figure 6c). Finally, the third experiment was nearly identical to the M. Benamara, X. Tong, Y. Wang, J. Chen, ACS Appl. Mater. Interfaces second one, except that the irradiation step was skipped (Figure 6b). In 2020, 12, 40067. all the experiments, additional setups using composite films that did not [7] W. Sim, R. T. Barnard, M. A. T. Blaskovich, Z. M. Ziora, Antibiotics contain iodine, lacking irradiation and/or not including the removal step 2018, 7, 93. were employed as controls. In all cases, the plates were examined to [8] U. Kadiyala, N. A. Kotov, J. S. VanEpps, Curr. Pharm. Des. 2018, 24, detect and measure (diameters) the growth-inhibition zones. 896. Statistical Analysis: Data from growth-inhibition diameters are [9] B. Wang, H. Liu, Z. Wang, S. Shi, K. Nan, Q. Xu, Z. Ye, H. Chen, expressed as the mean and SD. A repeated measure two-way ANOVA J. Mater. Chem. B 2017, 5, 1498. and Tukey’s multiple comparisons test were performed as appropriate, [10] D. Druvari, N. D. Koromilas, V. Bekiari, G. Bokias, J. K. Kallitsis, using GraphPad Prism version 6.00 (GraphPad Prism). Coatings 2018, 8, 8. [11] H. Deyhle, G. Schulz, B. Müller, R. H. French, R. H. French, M. E. Samberg, N. A. Monteiro-Riviere, S. Lanone, J. Boczkowski, Supporting Information M. S. Kim, K. Park, H. Tanaka, B. M. Finio, M. Karpelson, N. O. Pérez-Arancibia, P. S. Sreetharan, J. P. Whitney, R. J. Wood, Supporting Information is available from the Wiley Online Library or H. Schmitz, H. Soltner, H. Bousack, P. Graham, A. Philippides, from the author. P. Decuzzi, T.-L. Ren, Y.-F. Wang, Y. Yang, M. Lian, B. Srijanto, P. Mruetusatorn, et al., Encyclopedia of Nanotechnology, Springer, Netherlands 2012. Acknowledgements [12] A. N. Au-Duong, C. K. Lee, Mater. Sci. Eng., C 2017, 76, 477. [13] G. Mcdonnell, A. D. Russell, Clin. Microbiol. Rev. 1999, 12, 147. X.H. and G.B. contributed equally to this work. This work was supported [14] H. G. Brittain, Anal. Profiles Drug Subst. Excipients 2002, 29, 1. by the Spanish MINECO (project RTI2018-095622-B-I00, RTI2018- [15] H. Tsuchiya, T. Shirai, H. Nishida, H. Murakami, T. Kabata, 099965-B-I00, AEI/FEDER, UE), the Catalan AGAUR (project 2017 SGR N. Yamamoto, K. Watanabe, J. Nakase, J. Orthop. Sci. 2012, 17, 238, 2017 SGR 1431), and the ERC, under the EU-FP7 (ERC-Co 615954). 595. It was also funded by the CERCA Program/Generalitat de Catalunya. [16] G. Selvaggi, S. Monstrey, K. Van Landuyt, M. Hamdi, P. Blondeel, ICN2 is supported by the Severo Ochoa program from the Spanish Acta Chir. Belg. 2003, 103, 241. MINECO (Grant No. SEV-2017-0706). X.H. thanks the China Scholarship [17] D. F. Sava, K. W. Chapman, M. A. Rodriguez, J. A. Greathouse, Council (CSC) for scholarship support (201804910551). M.B. thanks the Polish National Agency for Academic Exchange (contract no. PPN/ P. S. Crozier, H. Zhao, P. J. Chupas, T. M. Nenoff, Chem. Mater. BEK/2018/1/00094/U/00001). 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