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MUC1-Targeted Cancer Cell Photothermal Ablation Using Bioinspired Gold Nanorods.

Zelasko-Leon DC, Fuentes CM, Messersmith PB - PLoS ONE (2015)

Bottom Line: MUC1-BSA-PD-NRs substantially decreased cell viability in photoirradiated MCF-7 cell lines vs.Agents exhibited no cytotoxicity in the absence of photothermal treatment.The facile nature of the coating method, combined with targeting and photoablation efficacy, are attractive features of these candidate cancer nanotherapeutics.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois, United States of America; Department of Bioengineering, University of California, Berkeley, Berkeley, California, United States of America.

ABSTRACT
Recent studies have highlighted the overexpression of mucin 1 (MUC1) in various epithelial carcinomas and its role in tumorigenesis. These mucins present a novel targeting opportunity for nanoparticle-mediated photothermal cancer treatments due to their unique antenna-like extracellular extension. In this study, MUC1 antibodies and albumin were immobilized onto the surface of gold nanorods using a "primer" of polydopamine (PD), a molecular mimic of catechol- and amine-rich mussel adhesive proteins. PD forms an adhesive platform for the deposition of albumin and MUC1 antibodies, achieving a surface that is stable, bioinert and biofunctional. Two-photon luminescence confocal and darkfield scattering imaging revealed targeting of MUC1-BSA-PD-NRs to MUC1+ MCF-7 breast cancer and SCC-15 squamous cell carcinoma cells lines. Treated cells were exposed to a laser encompassing the near-infrared AuNR longitudinal surface plasmon and assessed for photothermal ablation. MUC1-BSA-PD-NRs substantially decreased cell viability in photoirradiated MCF-7 cell lines vs. MUC1- MDA-MB-231 breast cancer cells (p < 0.005). Agents exhibited no cytotoxicity in the absence of photothermal treatment. The facile nature of the coating method, combined with targeting and photoablation efficacy, are attractive features of these candidate cancer nanotherapeutics.

No MeSH data available.


Related in: MedlinePlus

Schematic illustration of MUC1 antibody-conjugated gold NRs (anti-MUC1-BSA-PD-NRs) with a polydopamine adlayer and BSA coating.MUC1 antibodies serve as novel targeting constructs in the application of plasmonic photothermal therapy (A). Probing MUC1 targeting at underglycosylated N- and C-terminal domains in various epithelial carcinomas will expand our cancer-targeting repertoire with the potential for synergistic therapeutic effects (B, adapted from [12]).
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pone.0128756.g001: Schematic illustration of MUC1 antibody-conjugated gold NRs (anti-MUC1-BSA-PD-NRs) with a polydopamine adlayer and BSA coating.MUC1 antibodies serve as novel targeting constructs in the application of plasmonic photothermal therapy (A). Probing MUC1 targeting at underglycosylated N- and C-terminal domains in various epithelial carcinomas will expand our cancer-targeting repertoire with the potential for synergistic therapeutic effects (B, adapted from [12]).

Mentions: Here, we demonstrate the polydopamine-mediated (PD) conjugation of gold nanorods (AuNRs) with bovine serum albumin (BSA) and mucin 1 monoclonal antibodies (anti-MUC1) for passivation and targeting, respectively (Fig 1). The major goals of this work were to identify optimal conditions for nanoparticle functionalization and to demonstrate the feasibility of photothermal ablation of MUC1 positive cancer cells via biofunctionalized AuNRs. The results establish optimal conditions for surface modification of AuNRs with BSA and MUC1 antibody and physiologic stability. Successful targeting and photoablation of MUC1 positive cancer cells suggests these constructs may be useful anticancer therapeutics in the future.


MUC1-Targeted Cancer Cell Photothermal Ablation Using Bioinspired Gold Nanorods.

Zelasko-Leon DC, Fuentes CM, Messersmith PB - PLoS ONE (2015)

Schematic illustration of MUC1 antibody-conjugated gold NRs (anti-MUC1-BSA-PD-NRs) with a polydopamine adlayer and BSA coating.MUC1 antibodies serve as novel targeting constructs in the application of plasmonic photothermal therapy (A). Probing MUC1 targeting at underglycosylated N- and C-terminal domains in various epithelial carcinomas will expand our cancer-targeting repertoire with the potential for synergistic therapeutic effects (B, adapted from [12]).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493038&req=5

pone.0128756.g001: Schematic illustration of MUC1 antibody-conjugated gold NRs (anti-MUC1-BSA-PD-NRs) with a polydopamine adlayer and BSA coating.MUC1 antibodies serve as novel targeting constructs in the application of plasmonic photothermal therapy (A). Probing MUC1 targeting at underglycosylated N- and C-terminal domains in various epithelial carcinomas will expand our cancer-targeting repertoire with the potential for synergistic therapeutic effects (B, adapted from [12]).
Mentions: Here, we demonstrate the polydopamine-mediated (PD) conjugation of gold nanorods (AuNRs) with bovine serum albumin (BSA) and mucin 1 monoclonal antibodies (anti-MUC1) for passivation and targeting, respectively (Fig 1). The major goals of this work were to identify optimal conditions for nanoparticle functionalization and to demonstrate the feasibility of photothermal ablation of MUC1 positive cancer cells via biofunctionalized AuNRs. The results establish optimal conditions for surface modification of AuNRs with BSA and MUC1 antibody and physiologic stability. Successful targeting and photoablation of MUC1 positive cancer cells suggests these constructs may be useful anticancer therapeutics in the future.

Bottom Line: MUC1-BSA-PD-NRs substantially decreased cell viability in photoirradiated MCF-7 cell lines vs.Agents exhibited no cytotoxicity in the absence of photothermal treatment.The facile nature of the coating method, combined with targeting and photoablation efficacy, are attractive features of these candidate cancer nanotherapeutics.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, Chemistry of Life Processes Institute, Northwestern University, Evanston, Illinois, United States of America; Department of Bioengineering, University of California, Berkeley, Berkeley, California, United States of America.

ABSTRACT
Recent studies have highlighted the overexpression of mucin 1 (MUC1) in various epithelial carcinomas and its role in tumorigenesis. These mucins present a novel targeting opportunity for nanoparticle-mediated photothermal cancer treatments due to their unique antenna-like extracellular extension. In this study, MUC1 antibodies and albumin were immobilized onto the surface of gold nanorods using a "primer" of polydopamine (PD), a molecular mimic of catechol- and amine-rich mussel adhesive proteins. PD forms an adhesive platform for the deposition of albumin and MUC1 antibodies, achieving a surface that is stable, bioinert and biofunctional. Two-photon luminescence confocal and darkfield scattering imaging revealed targeting of MUC1-BSA-PD-NRs to MUC1+ MCF-7 breast cancer and SCC-15 squamous cell carcinoma cells lines. Treated cells were exposed to a laser encompassing the near-infrared AuNR longitudinal surface plasmon and assessed for photothermal ablation. MUC1-BSA-PD-NRs substantially decreased cell viability in photoirradiated MCF-7 cell lines vs. MUC1- MDA-MB-231 breast cancer cells (p < 0.005). Agents exhibited no cytotoxicity in the absence of photothermal treatment. The facile nature of the coating method, combined with targeting and photoablation efficacy, are attractive features of these candidate cancer nanotherapeutics.

No MeSH data available.


Related in: MedlinePlus