Delivery of chemotherapeutic drug targeting folate receptor to oral cancer cells using functionalized carbon nanospheres.

Folate receptor (FR) has long been the subject of active interest as regards its potential to serve as a target for cancer therapy. FR is overexpressed in several cancers, including clinical samples of different stages from Oral Squamous Cell Carcinoma (OSCC) patients. However, no clear correlation or conclusive finding has been obtained so far which might indicate the efficacy of FR as a credible target for the treatment of OSCC. 
Methods: All cell lines to be used were assessed for FR expression. Subsequently, we developed glucose-derived carbon nanospheres (CSPs) and primed them with a Folate-based cationic lipid FA8 and the chemotherapeutic drug doxorubicin (DOX). CSP-based delivery systems along with the pristine drug Doxorubicin were characterized and treated subsequently to in vitro cultures of OSCC cells and assessed for cancer cell targetability as well as cell death. Subsequently, treatment was administered to immunocompetent C57 mice carrying MOC2-based syngeneic OSCC tumors and assessed for tumor regression and toxicity.
Results: Ligand-primed targeted CSPs exhibited commendable drug uptake as well as efficient induction of cell death. Further, receptor-blocking studies revealed FR-mediated uptake, preferentially in cancer cells. Drug once delivered by ligand-primed CSPs was retained longer inside cells than the pristine drug alone, indicating possibilities of better therapeutic outcome. In animal studies, CSP-FA8-DOX (Ligand primed targeted CSP) demonstrated significant regression in tumor size compared to pristine Doxorubicin as well as CSP-DOX (non-targeted CSP) treated animals. 
Conclusions: FR-mediated system CFD demonstrated targeted drug uptake and apoptotic death selectively in cancer cells. Significant tumor regression was also observed in vivo. Overall, it may be presumed that the Folate receptor is a therapeutic target with substantial potential in OSCC treatment.
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