Function of gold nanoparticles in oral cancer beyond drug delivery: Implications in cell apoptosis.

OBJECTIVES: Gold nanoparticles (AuNPs) are used to deliver drugs and therapeutic small molecule inhibitors to cancer cells. Evidence shows that AuNPs coated with nuclear localization sequence can cross the nuclear membrane and induce cellular apoptosis. To determine the therapeutic role of AuNPs, we compared two nanoconstructs conjugated to doxorubicin (DOX) through pH-sensitive and pH-resistant linkers. MATERIALS AND METHODS: We tested DOX nanoconjugates' cytotoxicity, cellular and nuclear uptake in oral squamous cell carcinoma cell line. Furthermore, we evaluated the therapeutic effect of pH-sensitive and pH-resistant DOX bioconjugates in hamster buccal pouch carcinoma model. RESULTS: Our data indicate that pH-resistant and pH-sensitive DOX-nanoconjugates were equally localized in cancer cells, but the pH-resistant DOX nanoparticles were more localized in the nuclei inducing a 2-fold increase in the apoptotic effect compared with the pH-sensitive DOX nanoparticles. Our in vivo results show significantly higher tumor shrinkage and survival rates in animals treated with DOX pH-resistant AuNPs compared with pH-sensitive ones. CONCLUSION: Our findings suggest that AuNPs enhance the cytotoxic effect against cancer cells in addition to acting as drug carriers. DOX pH-resistant AuNPs enhanced accumulation of AuNPs in cancer cells' nuclei inducing a significant cellular apoptosis which was confirmed using in vitro and in vivo experiments without deleterious effects on blood cell count.

Therapeutic efficacy of plasmonic photothermal nanoparticles in hamster buccal pouch carcinoma.

OBJECTIVES: The objective of this study was to assess the short-term effect of plasmonic photothermal therapy (PPTT) on induced hamster buccal pouch (HBP) carcinoma. STUDY DESIGN: Seventy-six Syrian golden male hamsters were used. The induced HBP carcinomas were directly injected with ∼30 nm gold nanospheres followed by 15 min laser exposure (PPTT). RESULTS: PPTT caused rapid growth cessation and dramatic decrease in tumor sizes after 4 weeks of treatment (P < .05) compared to controls. Microscopic and immunohistochemical examination of the tumor biopsies revealed significant differences in the cellular apoptotic index (AI) value and proliferating cell nuclear antigen (PCNA) immunoexpression in PPTT-treated tumor tissue sections compared to controls (P < .05). Survival probability of the treated animals was increased compared to controls (P < .05). CONCLUSION: PPTT proved to be a successful method for treating superficially located HBP carcinomas.