Folate receptor-targeted thiol-maleimide clicked chitosan/carboxymethyl cellulose nanoparticles for cisplatin delivery in oral carcinoma.

This study aimed to develop cisplatin (CDDP)-loaded folic acid (FA)-decorated nanoparticles (NPs) as targeted drug carrier towards overexpressed folate receptors on the oral carcinoma cell line (KB cells). The FA-conjugated thiolated succinyl chitosan (FA-SH-SCS) and maleimide-grafted-carboxymethyl cellulose (CMC-MAL) were synthesized and acquired in the preparation of NPs via thiol-maleimide click reaction. The physicochemical characteristics, drug loading, and drug release of the FA-decorated NPs (FA-NPs) were examined. Also, the in vitro biocompatibility, cellular uptake, and cell death mechanism were investigated. Relatively spherical NPs with negative charge were obtained with a size of approximately 200 nm. The formation of FA-NPs through click reaction was confirmed by the pH change and Ellman's assay. The release of CDDP from the FA-NPs was influenced by the acidic tumor environment. The FA-NPs were non-toxic to the normal cells. Furthermore, FA-NPs improved the cellular uptake of CDDP in oral carcinoma cells through specific recognition of folate receptors by FA-NPs. The delivery of CDDP by FA-NPs to the KB cell induced the apoptotic cell death pathway. Therefore, FA-NPs presented the potential to be effective nanocarriers for CDDP delivery in the treatment of oral cancer via active targeting approach.