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

• Published in: Oral diseases 2021-03, Vol.27 (2), p.251-265
• Main Authors: Essawy, Marwa M., El‐Sheikh, Sahar M., Raslan, Hanaa S., Ramadan, Heba S., Kang, Bin, Talaat, Iman M., Afifi, Marwa M.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Cancer; Carcinoma, Squamous Cell - drug therapy; Cell Line, Tumor; Cytotoxicity; Doxorubicin; Drug Carriers; Drug delivery; Drug Delivery Systems; Gold; gold nanoparticles; hamster buccal pouch carcinoma; Hydrogen-Ion Concentration; Localization; Metal Nanoparticles; Mouth Neoplasms - drug therapy; Nanoparticles; Oral cancer; Oral squamous cell carcinoma; pH effects; Squamous cell carcinoma
• ISSN: 1354-523X; 1601-0825
• DOI: 10.1111/odi.13551

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.