Pharmaceutical Formulations Containing Graphene and 5-Fluorouracil for Light-Emitting Diode-Based Photochemotherapy of Skin Cancer
Sara I. Amaral, Filipa A. L. S. Silva, Raquel Costa‐Almeida, Licínia Timochenco, José R. Fernandes, Bruno Sarmento, Inês C. Gonçalves, Fernão D. Magalhães, Artur M. Pinto
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 sp 2 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.