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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

Quantification of breast and oral cancer photothermal therapy.Analysis of normalized viable cell areas reveals MUC1-dependent therapy vs. non-targeted BSA-PD-NRs in MCF-7 and SCC15 cell lines (* p < 0.05, ** p < 0.01, *** p < 0.001). Two-way ANOVA reveals a statistically significant impact of dose (p < 0.0001) and treatment (p < 0.0001). The interaction of dose and treatment was found to be statistically significant only for MCF-7 cells (p < 0.001).
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pone.0128756.g007: Quantification of breast and oral cancer photothermal therapy.Analysis of normalized viable cell areas reveals MUC1-dependent therapy vs. non-targeted BSA-PD-NRs in MCF-7 and SCC15 cell lines (* p < 0.05, ** p < 0.01, *** p < 0.001). Two-way ANOVA reveals a statistically significant impact of dose (p < 0.0001) and treatment (p < 0.0001). The interaction of dose and treatment was found to be statistically significant only for MCF-7 cells (p < 0.001).

Mentions: The overall impact on MCF-7 cells was most profound, in accordance with the high carcinoma-associated MUC1 expression observed via flow cytometry. Treatment with MUC1-C-BSA-PD-NR followed similar trends. Because cell death was accompanied by delamination under the conditions of our experiments (Fig I in S1 File), analysis of normalized viable cell areas was used for quantification, revealing MUC1-dependent cell death in anti-MUC1 modified AuNRs vs. non-targeted BSA-PD-NRs in MCF-7 and SCC15 cell lines (* p < 0.001). Two-way ANOVA indicates a statistically significant impact of dose (p < 0.0001) and treatment (p < 0.0001). Photoablation was observed at lower doses in MCF-7 vs. SCC15 cells (Fig G in S1 File), a result that is consistent with their differential MUC1 expression profiles (Fig F in S1 File). MUC1-deficient MDA-MB-231 cell lines did not present any pattern of photoablation upon NIR exposure, nor was viability negatively impacted in non-photoirradiated control samples (Fig 7).


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

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

Quantification of breast and oral cancer photothermal therapy.Analysis of normalized viable cell areas reveals MUC1-dependent therapy vs. non-targeted BSA-PD-NRs in MCF-7 and SCC15 cell lines (* p < 0.05, ** p < 0.01, *** p < 0.001). Two-way ANOVA reveals a statistically significant impact of dose (p < 0.0001) and treatment (p < 0.0001). The interaction of dose and treatment was found to be statistically significant only for MCF-7 cells (p < 0.001).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0128756.g007: Quantification of breast and oral cancer photothermal therapy.Analysis of normalized viable cell areas reveals MUC1-dependent therapy vs. non-targeted BSA-PD-NRs in MCF-7 and SCC15 cell lines (* p < 0.05, ** p < 0.01, *** p < 0.001). Two-way ANOVA reveals a statistically significant impact of dose (p < 0.0001) and treatment (p < 0.0001). The interaction of dose and treatment was found to be statistically significant only for MCF-7 cells (p < 0.001).
Mentions: The overall impact on MCF-7 cells was most profound, in accordance with the high carcinoma-associated MUC1 expression observed via flow cytometry. Treatment with MUC1-C-BSA-PD-NR followed similar trends. Because cell death was accompanied by delamination under the conditions of our experiments (Fig I in S1 File), analysis of normalized viable cell areas was used for quantification, revealing MUC1-dependent cell death in anti-MUC1 modified AuNRs vs. non-targeted BSA-PD-NRs in MCF-7 and SCC15 cell lines (* p < 0.001). Two-way ANOVA indicates a statistically significant impact of dose (p < 0.0001) and treatment (p < 0.0001). Photoablation was observed at lower doses in MCF-7 vs. SCC15 cells (Fig G in S1 File), a result that is consistent with their differential MUC1 expression profiles (Fig F in S1 File). MUC1-deficient MDA-MB-231 cell lines did not present any pattern of photoablation upon NIR exposure, nor was viability negatively impacted in non-photoirradiated control samples (Fig 7).

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