TYPE Editorial PUBLISHED 05 September 2022 DOI 10.3389/fbioe.2022.1018014 Editorial: High added-value OPEN ACCESS nanoparticles: Rethinking and EDITED AND REVIEWED BY Gianni Ciofani, Italian Institute of Technology (IIT), Italy recycling cell protein waste *CORRESPONDENCE Joaquin Seras-Franzoso, Ugutz Unzueta 1,2,3, Julieta M. Sanchez 3,4†, Elena Garcia-Fruitós 5 joaquin.seras@vhir.org and Joaquin Seras-Franzoso 3,6* † PRESENT ADDRESS 1 Julieta M. Sanchez, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain, 2Josep Carreras Leukaemia Institut de Biotecnologia i de Research Institute (IJC, Campus Sant Pau), Barcelona, Spain, 3CIBER de Bioingeniería, Biomateriales y Biomedicina (IBB), Universitat Nanomedicina (CIBER-BBN), Instituto de Salud Carlos III, Madrid, Spain, 4Instituto de Investigaciones Autònoma de Barcelona, Bellaterra, Biológicas y Tecnológicas (IIByT), CONICET- Universidad Nacional de Córdoba, ICTA, FCEFyN, UNC, Spain Córdoba, Argentina, 5Department of Ruminant Production, Institute of Agrifood Research and Technology (IRTA), Caldes de Montbui, Spain, 6Drug Delivery and Targeting, Vall d’Hebron Institute of SPECIALTY SECTION Research (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain This article was submitted to Nanobiotechnology, a section of the journal KEYWORDS Frontiers in Bioengineering and Biotechnology nanobiotechnlogy, biomedicine, green biotechnology, Inclusion bodies (IBs), Extracellular vesicles (EVs), virus-based nanomaterials RECEIVED 12 August 2022 ACCEPTED 15 August 2022 PUBLISHED 05 September 2022 CITATION Unzueta U, Sanchez JM, Garcia-Fruitós E and Seras-Franzoso J Editorial on the Research Topic (2022), Editorial: High added-value High added-value nanoparticles: Rethinking and recycling cell protein nanoparticles: Rethinking and recycling waste cell protein waste. Front. Bioeng. Biotechnol. 10:1018014. doi: 10.3389/fbioe.2022.1018014 COPYRIGHT Nanotechnology, and specifically the use of nanoparticles (NPs), has been intensively © 2022 Unzueta, Sanchez, Garcia- explored during the recent decades in order to solve unmet clinical needs and face Fruitós and Seras-Franzoso. This is an open-access article distributed under different biotechnological challenges. However, their success has been rather modest due the terms of the Creative Commons to several limitations associated with the use of current nanomaterials. In this sense, one of Attribution License (CC BY). The use, distribution or reproduction in other the aspects in which current NPs have failed is in the development of complex forums is permitted, provided the formulations, including biological cues in/onto their surface in a cost-effective original author(s) and the copyright manner. Moreover, the potential toxicity of the chemicals used for NP synthesis is owner(s) are credited and that the original publication in this journal is still an important safety and environmental concern that prevents the implementation of cited, in accordance with accepted many of such formulations. In this scenario, naturally occurring NPs offer a unique academic practice. No use, distribution or reproduction is permitted which does opportunity to overcome these biocompatibility, efficacy and cost-effectiveness issues. not comply with these terms. Production of naturally occurring NPs, synthesized either directly within living cells or biofabricated through the application of biological catalyzers, have become an appealing source of NPs with value in the biomedical and biotechnological fields. Such technologies provide unique insights, enabling the preparation of complex nano- sized systems, e.g., Inclusion bodies (IBs) or extracellular vesicles (EVs), formed by a milieu of active biomolecules, in relatively simple ways while rendering highly biocompatible interfaces, optimal for their use in biomedicine. In addition, the diversity in composition and structure of naturally originated NPs empower a significant number of distinct applications also in the biotechnological field, such as their use as immobilized biocatalysts or as biosensors for a spectrum of analytes. This diversity is further fueled by the capacity of tailoring natural NPs structure and Frontiers in Bioengineering and Biotechnology 01 frontiersin.org Unzueta et al. 10.3389/fbioe.2022.1018014 functionality in a bottom-up approach via the genetic of how biological systems can be efficiently used as catalyzers for modification of the biological factories. Among the most the biosynthesis of inorganic NPs from externally sourced metal common naturally occurring NPs we can find protein-only ions, avoiding the use of hazardous chemicals generally employed NPs, IBs, virus-like particles (VLPs), vaults, EVs, in the production of such materials. Moreover, AgNPs, magnetosomes or polymeric particles (PP). Besides, a variety biofabricated in this fashion, can additionally incorporate plant- of metallic NPs can also benefit from the use of bio-catalyzers derived phytochemicals, conferring novel antioxidant properties during their fabrication. In this regard, the implementation of and expanding thus, the spectrum of biological applications of greener synthesis processes is of paramount importance in the generated nanomaterials. actual context of global environmental crisis. Another example of green biotechnology is collected here by Concerning the biomedical context, biocompatibility is one the virus-based nanomaterials generated by McNulty et al. as of the basic traits that any NP must comply with in order to have reagents for therapeutic protein purification. In this work, virus- a chance to progress towards its clinical use. In this sense, based immunosorbent nanoparticles, generated using plant- Barguilla et al. validated IBs as sub-micron protein particles based manufacturing and virus-functionalized magnetic displaying no cytotoxicity, genotoxicity or oxidative stress over particles were shown as a potential alternative to the Caco-2 cells, irrespective of the prokaryotic cell factory employed traditional chemical methods used in the biopharmaceutical for their biofabrication. Such reports are very helpful in order to industry. Of note, such assemblies showed an extraordinary elaborate future product safety profiles and gain insight on the binding affinity capacity for therapeutic proteins. NP/cell interplay. In the same line, but approaching the potential Finally, a novel usage for bacterial IBs as potential biosensors toxicity of NPs from a structural perspective, Gil-Garcia and has been described by Hrabarova etal. This work is yet another Ventura reviewed an intriguing strategy to drive IB formation example of the enormous potential exhibited by cell protein while avoiding the use of potentially toxic amyloid-like domains waste NPs to be re-formulated in order to achieve new objectives. to pull down proteins into valuable NPs. Thus, standard In this regard, the authors successfully engineered a highly recombinant manipulation would allow to replace the amyloid soluble green fluorescent protein to produce bioactive IBs (highly beta) conformation of natural IBs by a coiled-coil fold, with an increased sensitivity to metals and di-/tri-inorganic composed of two or more α-helices. This last protein motif is phosphates. Their approach was based on the addition of widely used by nature to create supramolecular assemblies and small aggregation-prone peptide tags that also show modified could reduce potential undesired side effects derived from the sensitivity for poly-phosphates and metals ions. Thus, the same amyloid nature of IBs. Nevertheless, numerous studies reported type of biosensors could be used to detect the presence of metal no evident toxicity caused by IBs after challenging cell or animal ions such as Cu2+, Zn2+ or Hg2+ in environmental samples or to models (de Marco et al., 2019) and potential IB derived monitor pyrophosphates levels in plasma, which possess value as cytotoxicity seems to be linked to specific polypeptide a biomarker for various diseases. sequences and aggregation status (González-Montalbán et al., All in all, the present research topic reflects the growing 2007). interest of natural NPs for different biomedical and Of note, the notorious biocompatibility exhibited by IBs is biotechnological purposes, where novel applications are shared by other types of naturally occurring NPs such as EVs. In steadily appearing and main limitations, e.g., toxicity studies, this regard, EVs are cell membrane bound vesicles secreted by are being tackled. However, some issues such as: standardization virtually any cell type that can be exploited as efficient delivery of natural NPs characterization, cumbersome scaling up systems as exemplified by Dong etal. In this instance, the authors processes or further understanding of body responses to long took advantage of EVs properties as natural nanosized drug delivery term exposure should still be addressed in order to fully fulfill the platforms to envisage an original application for EVs derived from promise of such NPs. fetal bovine serum (FBS). Serum is a biological fluid extremely rich in EVs and therefore a very interesting source for isolating these NPs in enough amounts. Thus, FBS-derived EVs were functionalized Author contributions with Icariin as an alternative way to promote osteoblast proliferation and bone regeneration in vitro, significantly increasing the observed JS-F and UU prepared the first draft. All the authors activity compared to Icariin alone. contributed to and revised the final manuscript. With respect to the use of natural NPs in green biotechnology, the present issue also includes diverse and interesting contributions. Shahzadi etal. presented a representative work Conflict of interest where spherical silver nanoparticles (AgNPs), with different antioxidant, cytotoxic and antimicrobial activities, were JS-F, EG-F, UU, and JS all hold pending or confirmed efficiently generated in a cost-effective and environmentally patents. UU patents are licensed to the start-up company friendly process using plant biotechnology. This is an example Nanoligent, SL. Frontiers in Bioengineering and Biotechnology 02 frontiersin.org Unzueta et al. 10.3389/fbioe.2022.1018014 Publisher’s note organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or All claims expressed in this article are solely those of the claim that may be made by its manufacturer, is not guaranteed or authors and do not necessarily represent those of their affiliated endorsed by the publisher. References de Marco, A., Ferrer-Miralles, N., Garcia-Fruitós, E., Mitraki, A., Peternel, S., González-Montalbán, N., Villaverde, A., and Aris, A. (2007). Amyloid-linked Rinas, U., et al. (2019). Bacterial inclusion bodies are industrially exploitable cellular toxicity triggered by bacterial inclusion bodies. Biochem. Biophys. Res. amyloids. FEMS Microbiol. Rev. 43, 53–72. [Internet]Available at: doi:10.1093/ Commun. 355, 637–642. [Internet]Available from:. doi:10.1016/j.bbrc.2007. femsre/fuy038 01.192 Frontiers in Bioengineering and Biotechnology 03 frontiersin.org