The theranostic potentialities of bioavailable nanocurcumin in oral cancer management.

BACKGROUND: Oral cancer, one of the most common cancers, has unimproved 5-years survival rate in the last 30 years and the chemo/radiotherapy-associated morbidity. Therefore, intervention strategies that evade harmful side effects of the conventional treatment modalities are of need. Herbal therapy as a complementary preventive/therapeutic modality has gained attention. Curcumin is one of the herbal compounds possessing unique anticancer activity and luminescent optical properties. However, its low water solubility limits its efficacy. In contrast, curcumin at the nanoscale shows altered physical properties with enhancing bioavailability. METHODS: The current study evaluated the impact of nanocurcumin as an anti-oral cancer herbal remedy, comparing its efficacy against the native curcumin complement and conventional chemotherapeutic. An optimized polymeric-stabilized nanocurcumin was synthesized using the solvent-antisolvent precipitation technique. After assuring the solubility and biocompatibility of nanocurcumin, we determined its cytotoxic dose in treating the squamous cell carcinoma cell line. We then evaluated the anti-tumorigenic activity of the nano-herb in inhibiting wound closure and the cytological alterations of the treated cancer cells. Furthermore, the cellular uptake of the nanocurcumin was assessed depending on its autofluorescence. RESULTS: The hydrophilic optimized nanocurcumin has a potent cancerous cytotoxicity at a lower dose (60.8 µg/mL) than the native curcumin particles (212.4 µg/mL) that precipitated on high doses hindering their cellular uptake. Moreover, the nanocurcumin showed differential targeting of the cancer cells over the normal fibroblasts with a selectivity index of 4.5. With the confocal microscopy, the luminescent nanoparticles showed gradual nuclear and cytoplasmic uptake with apparent apoptotic cell death, over the fluorescent doxorubicin with its necrotic effect. Furthermore, the nanocurcumin superiorly inhibited the migration of cancer cells by -25%. CONCLUSIONS: The bioavailable nanocurcumin has better apoptotic cytotoxicity. Moreover, its superior luminescence promotes the theranostic potentialities of the nano-herb combating oral cancer.

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.