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 lightto-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.

New MoS2/Tegafur-Containing Pharmaceutical Formulations for Selective LED-Based Skin Cancer Photo-Chemotherapy

“…Mild PTT strategies include a temperature increase to 39–45 °C, as cancer cells are less tolerant to heat stress; this therapeutic approach should present selectivity. The increase in temperature drastically reduces DNA and RNA synthesis, as well as DNA repair, and increases the permeability of tumor cells, leading to an increase in drug and nanomaterial intake [ 90 , 91 ]. The optimization of this effect should destroy the A-431 skin carcinoma cells without killing the normal HFF-1 skin fibroblasts.…”

“…Mild PTT strategies involve increasing the temperature to between 39 and 45 °C, affecting mainly tumor cells, because they are less tolerant to heat stress. It inhibits DNA and RNA synthesis, as well as DNA repair, while tumor cell membranes become more permeable, improving drug and nanomaterial intake [ 90 , 91 ]. This strategy has been used to enhance chemotherapy effects.…”

“…This strategy has been used to enhance chemotherapy effects. Above 60 °C, cell necrosis occurs through thermal ablation [ 90 , 91 , 95 ].…”

Titania–Graphene Oxide Nanocomposite-Based Philadelphia-Positive Leukemia Therapy

“…GO is fabricated by the oxidation of graphite and offers a robust scaffold for drug delivery by containing hydroxyl, carboxyl, and other reactive groups on its surface for successful drug and ligand conjugation . GO alone and its combination with other elements have been widely employed in drug delivery, − diagnosis and biosensing, , antibacterials, and tissue regeneration and engineering. , For instance, graphene quantum dots and titanate nanoflowers have been employed to deliver doxorubicin to HER2-expressing cancer cells. Meanwhile, the graphene quantum dots could simultaneously help locate the drug accumulation intracellularly by fluorescence tracking .…”