Pharmaceutical Formulations Containing Graphene and 5-Fluorouracil for Light-Emitting Diode-Based Photochemotherapy of Skin Cancer.

ABSTRACT

Nonmelanoma skin cancer (NMSC) is the most common cancer worldwide, among which 80% is basal cell carcinoma (BCC). Current therapies' low efficacy, side effects, and high recurrence highlight the need for alternative treatments. In this work, a partially reduced nanographene oxide (p-rGOn) developed in our laboratory was used. It has been achieved through a controlled reduction of nanographene oxide via UV-C irradiation that yields small nanometric particles (below 200 nm) that preserve the original water stability while acquiring high light-to-heat conversion efficiency. The latter is explained by a loss of carbon-oxygen single bonds (C-O) and the re-establishment of sp2 carbon bonds. p-rGOn was incorporated into a Carbopol hydrogel together with the anticancer drug 5-fluorouracil (5-FU) to evaluate a possible combined PTT and chemotherapeutic effect. Carbopol/p-rGOn/5-FU hydrogels were considered noncytotoxic toward normal skin cells (HFF-1). However, when A-431 skin cancer cells were exposed to NIR irradiation for 30 min in the presence of Carbopol/p-rGOn/5-FU hydrogels, almost complete eradication was achieved after 72 h, with a 90% reduction in cell number and 80% cell death of the remaining cells after a single treatment. NIR irradiation was performed with a light-emitting diode (LED) system, developed in our laboratory, which allows adjustment of applied light doses to achieve a safe and selective treatment, instead of the standard laser systems that are associated with damages in the healthy tissues in the tumor surroundings. Those are the first graphene-based materials containing pharmaceutical formulations developed for BCC phototherapy.