d88d102db7c8cc74c32b02847a2aee07 IntJouMol_a2022v23p13109.pdf 2228ab3ecaabf7348c530848650e20815d8a00d0 IntJouMol_a2022v23p13109.pdf d42d2d605b53b37f1f1879bc418f276277d4f731133b287b4e1b4768867a06b3 IntJouMol_a2022v23p13109.pdf Title: Hybrid Gold Nanorod-Based Nanoplatform with Chemo and Photothermal Activities for Bimodal Cancer Therapy Subject: Metal nanoparticles (NPs), particularly gold nanorods (AuNRs), appear as excellent platforms not only to transport and deliver bioactive cargoes but also to provide additional therapeutic responses for diseased cells and tissues and/or to complement the action of the carried molecules. In this manner, here, we optimized a previous developed metal-based nanoplatform composed of an AuNR core surrounded by a polymeric shell constructed by means of the layer-by-layer approach, and in which very large amounts of the antineoplasic drug doxorubicin (DOXO) in a single loading step and targeting capability thanks to an outer hyaluronic acid layer were incorporated by means of an optimized fabrication process (PSS/DOXO/PLL/HA-coated AuNRs). The platform retained its nanometer size with a negative surface charge and was colloidally stable in a range of physiological conditions, in which only in some of them some particle clustering was noted with no precipitation. In addition, the dual stimuli-responsiveness of the designed nanoplatform to both endogenous proteases and external applied light stimuli allows to perfectly manipulate the chemodrug release rates and profiles to achieve suitable pharmacodynamics. It was observed that the inherent active targeting abilities of the nanoplatfom allow the achievement of specific cell toxicity in tumoral cervical HeLa cells, whilst healthy ones such as 3T3-Balb fibroblast remain safe and alive in agreement with the detected levels of internalization in each cell line. In addition, the bimodal action of simultaneous chemo- and photothermal bioactivity provided by the platform largely enhances the therapeutic outcomes. Finally, it was observed that our PSS/DOXO/PLL/HA-coated AuNRs induced cell mortality mainly through apoptosis in HeLa cells even in the presence of NIR light irradiation, which agrees with the idea of the chemo-activity of DOXO predominating over the photothermal effect to induce cell death, favoring an apoptotic pathway over necrosis for cell death. Keywords: gold nanorods; layer assembly; photothermal therapy; multimodal therapy; cell death pathway Author: Lilia Arellano-Galindo, Eva Villar-Alvarez, Alejandro Varela, Valeria Figueroa, Javier Fernandez-Vega, Adriana Cambón, Gerardo Prieto, Silvia Barbosa and Pablo Taboada Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Nov 8 06:23:26 2022 CET ModDate: Tue Nov 8 06:33:57 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 25 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 5443260 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- SOZKOC+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 ORWJHQ+VnURWPalladioL Type 1 Custom yes yes no 15 0 QUGYLM+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 QWTBZH+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 PMDMCH+URWPalladioL-Ital Type 1 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(Rel. 1.22.1, 2019-04-17) Date: 2023-09-27 02:38:28 CEST RepresentationInformation: IntJouMol_a2022v23p13109.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2023-09-26 18:15:56 CEST Size: 5443260 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 632 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Results and Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Children: Item: Title: Synthesis and Photothermal Characterization of the Metallic Cores Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Functionalization, Colloidal Stability and Photothermal Conversion of the Metallic Platform Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: DOXO Release Profiles Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: In Vitro Biological Evaluation Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Children: Item: Title: Materials Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Synthesis of AuNRs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: LbL Polymeric Coating of AuNRs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Nanoplatform Characterization Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Children: Item: Title: Dynamic Light Scattering (DLS) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Electrophoretic Mobilities Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Transmission Electron Microscopy (TEM) Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: NIR-Laser Induced Photothermal Effect of AuNRs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: Colloidal Stability of AuNRs Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Item: Title: Nanoplatform Characterization Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4eb7f003 Item: Title: In Vitro DOXO Release Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@eafc191 Item: Title: Tumor Cells Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612fc6eb Item: Title: Cellular Uptake Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1060b431 Item: Title: In Vitro Cell Citotoxicity Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@612679d6 Item: Title: Cell Death Mechanism Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@11758f2a Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@e720b71 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1b26f7b2 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@491cc5c9 Info: Title: Hybrid Gold Nanorod-Based Nanoplatform with Chemo and Photothermal Activities for Bimodal Cancer Therapy Author: Lilia Arellano-Galindo, Eva Villar-Alvarez, Alejandro Varela, Valeria Figueroa, Javier Fernandez-Vega, Adriana Cambón, Gerardo Prieto, Silvia Barbosa and Pablo Taboada Subject: Metal nanoparticles (NPs), particularly gold nanorods (AuNRs), appear as excellent platforms not only to transport and deliver bioactive cargoes but also to provide additional therapeutic responses for diseased cells and tissues and/or to complement the action of the carried molecules. In this manner, here, we optimized a previous developed metal-based nanoplatform composed of an AuNR core surrounded by a polymeric shell constructed by means of the layer-by-layer approach, and in which very large amounts of the antineoplasic drug doxorubicin (DOXO) in a single loading step and targeting capability thanks to an outer hyaluronic acid layer were incorporated by means of an optimized fabrication process (PSS/DOXO/PLL/HA-coated AuNRs). The platform retained its nanometer size with a negative surface charge and was colloidally stable in a range of physiological conditions, in which only in some of them some particle clustering was noted with no precipitation. In addition, the dual stimuli-responsiveness of the designed nanoplatform to both endogenous proteases and external applied light stimuli allows to perfectly manipulate the chemodrug release rates and profiles to achieve suitable pharmacodynamics. It was observed that the inherent active targeting abilities of the nanoplatfom allow the achievement of specific cell toxicity in tumoral cervical HeLa cells, whilst healthy ones such as 3T3-Balb fibroblast remain safe and alive in agreement with the detected levels of internalization in each cell line. In addition, the bimodal action of simultaneous chemo- and photothermal bioactivity provided by the platform largely enhances the therapeutic outcomes. Finally, it was observed that our PSS/DOXO/PLL/HA-coated AuNRs induced cell mortality mainly through apoptosis in HeLa cells even in the presence of NIR light irradiation, which agrees with the idea of the chemo-activity of DOXO predominating over the photothermal effect to induce cell death, favoring an apoptotic pathway over necrosis for cell death. 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583, 544, 594 Annotation: Subtype: Link Rect: 161, 561, 198, 571 Annotation: Subtype: Link Rect: 59, 527, 96, 537 Annotation: Subtype: Link Rect: 486, 503, 523, 514 Annotation: Subtype: Link Rect: 176, 481, 213, 491 Annotation: Subtype: Link Rect: 131, 458, 168, 468 Checksum: 5aac8588 Type: CRC32 Checksum: d88d102db7c8cc74c32b02847a2aee07 Type: MD5 Checksum: 2228ab3ecaabf7348c530848650e20815d8a00d0 Type: SHA-1