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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

Two-photon luminescence imaging.Two-photon luminescence (TPL) confocal imaging of MCF-7 and MDA-MB-231 breast cancer cells 24 h post treatment with NRs. Brightfield (BF, grayscale) and AuNR TPL images (red) reveal specific targeting in MUC1+ MCF-7 cells. Scale bar = 50 μm.
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pone.0128756.g004: Two-photon luminescence imaging.Two-photon luminescence (TPL) confocal imaging of MCF-7 and MDA-MB-231 breast cancer cells 24 h post treatment with NRs. Brightfield (BF, grayscale) and AuNR TPL images (red) reveal specific targeting in MUC1+ MCF-7 cells. Scale bar = 50 μm.

Mentions: Two-photon luminescence (TPL) imaging of MCF-7 breast cancer cells was pursued following treatment with 3 pM AuNRs (Fig 4). No non-specific cell uptake was observed with BSA-PD-NR, in contrast to BSA-NR. Additionally, enhanced cell colocalization was observed with treatment of MUC1-N- and MUC1-C BSA-PD-NR conjugates. In contrast, imaging of MUC1-deficient MDA-MB-231 breast cancer cells demonstrated no targeting of MUC1-conjugated BSA-PD-NRs and some non-specific uptake of BSA-NRs. In addition to the excellent analytical contrast afforded by TPL imaging, AuNRs are efficient scatterers of incident light, a phenomenon that can be exploited for contrast imaging via darkfield microscopy. Both MCF-7 and SCC15 cells demonstrate enhanced labeling with MUC1-modified BSA-PD-NRs vs. unmodified BSA-PD-NRs (Fig 5). In contrast, some uptake of BSA-NRs was detected in all cell lines regardless of MUC1 status, suggesting that the passivation of the NR surface in the absence of PD is incomplete or is susceptible to displacement.


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

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

Two-photon luminescence imaging.Two-photon luminescence (TPL) confocal imaging of MCF-7 and MDA-MB-231 breast cancer cells 24 h post treatment with NRs. Brightfield (BF, grayscale) and AuNR TPL images (red) reveal specific targeting in MUC1+ MCF-7 cells. Scale bar = 50 μm.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0128756.g004: Two-photon luminescence imaging.Two-photon luminescence (TPL) confocal imaging of MCF-7 and MDA-MB-231 breast cancer cells 24 h post treatment with NRs. Brightfield (BF, grayscale) and AuNR TPL images (red) reveal specific targeting in MUC1+ MCF-7 cells. Scale bar = 50 μm.
Mentions: Two-photon luminescence (TPL) imaging of MCF-7 breast cancer cells was pursued following treatment with 3 pM AuNRs (Fig 4). No non-specific cell uptake was observed with BSA-PD-NR, in contrast to BSA-NR. Additionally, enhanced cell colocalization was observed with treatment of MUC1-N- and MUC1-C BSA-PD-NR conjugates. In contrast, imaging of MUC1-deficient MDA-MB-231 breast cancer cells demonstrated no targeting of MUC1-conjugated BSA-PD-NRs and some non-specific uptake of BSA-NRs. In addition to the excellent analytical contrast afforded by TPL imaging, AuNRs are efficient scatterers of incident light, a phenomenon that can be exploited for contrast imaging via darkfield microscopy. Both MCF-7 and SCC15 cells demonstrate enhanced labeling with MUC1-modified BSA-PD-NRs vs. unmodified BSA-PD-NRs (Fig 5). In contrast, some uptake of BSA-NRs was detected in all cell lines regardless of MUC1 status, suggesting that the passivation of the NR surface in the absence of PD is incomplete or is susceptible to displacement.

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