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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

Bovine serum albumin (BSA) coating on polydopamine-primed gold NRs.(A) Electron microscopy of BSA-PD-NRs in secondary electron mode. Scale bar = 600 nm; Inset = 50 nm; (B) Circular dichroism of modified vs. unmodified gold NRs. BSA-modified NRs were modified with 10 or 20 mg/mL BSA, as indicated. The concentration of the BSA control was 0.25 mg/mL. Protein denaturation into β-sheet formation is indicated on PD-treated NRs modified with a sub-optimal concentration of BSA. Otherwise, BSA secondary structure is preserved, as quantified by the respective α-helical propensity of each modification.
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pone.0128756.g002: Bovine serum albumin (BSA) coating on polydopamine-primed gold NRs.(A) Electron microscopy of BSA-PD-NRs in secondary electron mode. Scale bar = 600 nm; Inset = 50 nm; (B) Circular dichroism of modified vs. unmodified gold NRs. BSA-modified NRs were modified with 10 or 20 mg/mL BSA, as indicated. The concentration of the BSA control was 0.25 mg/mL. Protein denaturation into β-sheet formation is indicated on PD-treated NRs modified with a sub-optimal concentration of BSA. Otherwise, BSA secondary structure is preserved, as quantified by the respective α-helical propensity of each modification.

Mentions: Modification of AuNRs with PD was performed as described previously [56, 57], yielding AuNRs surrounded by a thin PD coating. The presence of PD was confirmed by UV-vis red shift (Fig A in S1 File). PD-NRs were found to aggregate in buffer, but redispersion in BSA solution and isolation by centrifugation led to stable dispersions of BSA-PD-NRs. Using the solution AuNR LSPR intensity and peak shift (Fig B in S1 File) analyzed via UV-Vis-NIR spectrophotometry as a measure of NR stability, screening of a range of BSA concentrations (0–30 mg/mL) used in the two-step coating method led to the identification of an optimal protocol consisting of 0.1 mg/mL dopamine for PD coating of CTAB-NRs followed by stabilization in ≥10 mg/ml BSA. Under these optimal conditions, aggregation of BSA-PD-NRs was seven-fold less compared to PD-NRs (Fig B in S1 File). All subsequent experiments were performed on PD-NRs modified at 20 mg/mL BSA in order to ensure full passivation of the PD underlayer that may otherwise serve to promote AuNR aggregation. AuNRs (20 x 60 nm) modified with PD and BSA (20 mg/mL) were imaged via TEM following counterstaining with phosphotungstic acid to provide contrast for the organic BSA layer. A layer measuring ~15 nm in thickness was visualized on well-separated BSA-PD-NRs in SE mode (Fig 2A). The attenuation of XPS Au4f signal of a gold surface observed upon exposure to dopamine and BSA is consistent with the deposition of a PD coating followed by grafting of BSA (Fig C in S1 File).


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

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

Bovine serum albumin (BSA) coating on polydopamine-primed gold NRs.(A) Electron microscopy of BSA-PD-NRs in secondary electron mode. Scale bar = 600 nm; Inset = 50 nm; (B) Circular dichroism of modified vs. unmodified gold NRs. BSA-modified NRs were modified with 10 or 20 mg/mL BSA, as indicated. The concentration of the BSA control was 0.25 mg/mL. Protein denaturation into β-sheet formation is indicated on PD-treated NRs modified with a sub-optimal concentration of BSA. Otherwise, BSA secondary structure is preserved, as quantified by the respective α-helical propensity of each modification.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0128756.g002: Bovine serum albumin (BSA) coating on polydopamine-primed gold NRs.(A) Electron microscopy of BSA-PD-NRs in secondary electron mode. Scale bar = 600 nm; Inset = 50 nm; (B) Circular dichroism of modified vs. unmodified gold NRs. BSA-modified NRs were modified with 10 or 20 mg/mL BSA, as indicated. The concentration of the BSA control was 0.25 mg/mL. Protein denaturation into β-sheet formation is indicated on PD-treated NRs modified with a sub-optimal concentration of BSA. Otherwise, BSA secondary structure is preserved, as quantified by the respective α-helical propensity of each modification.
Mentions: Modification of AuNRs with PD was performed as described previously [56, 57], yielding AuNRs surrounded by a thin PD coating. The presence of PD was confirmed by UV-vis red shift (Fig A in S1 File). PD-NRs were found to aggregate in buffer, but redispersion in BSA solution and isolation by centrifugation led to stable dispersions of BSA-PD-NRs. Using the solution AuNR LSPR intensity and peak shift (Fig B in S1 File) analyzed via UV-Vis-NIR spectrophotometry as a measure of NR stability, screening of a range of BSA concentrations (0–30 mg/mL) used in the two-step coating method led to the identification of an optimal protocol consisting of 0.1 mg/mL dopamine for PD coating of CTAB-NRs followed by stabilization in ≥10 mg/ml BSA. Under these optimal conditions, aggregation of BSA-PD-NRs was seven-fold less compared to PD-NRs (Fig B in S1 File). All subsequent experiments were performed on PD-NRs modified at 20 mg/mL BSA in order to ensure full passivation of the PD underlayer that may otherwise serve to promote AuNR aggregation. AuNRs (20 x 60 nm) modified with PD and BSA (20 mg/mL) were imaged via TEM following counterstaining with phosphotungstic acid to provide contrast for the organic BSA layer. A layer measuring ~15 nm in thickness was visualized on well-separated BSA-PD-NRs in SE mode (Fig 2A). The attenuation of XPS Au4f signal of a gold surface observed upon exposure to dopamine and BSA is consistent with the deposition of a PD coating followed by grafting of BSA (Fig C in S1 File).

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