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Non-melanoma skin cancer (NMSC) is one of the most common types of cancer worldwide. Despite the low mortality rate, rising incidence and recurrence rates are a burden on healthcare systems. Standard treatments such as chemotherapy, radiotherapy, and surgery are either invasive or toxic to healthy tissues; therefore, new, alternative, selective treatments are needed. In this work, a combined photothermal and chemotherapeutic approach is proposed. MoS2 was used as photothermal agent. It was prepared by a liquid-phase exfoliation and intercalation method using polyvinylpyrrolidone (PVP), followed by recirculation through a custom-built high-power ultrasonication probe. After 6 h of ultrasonication treatment, the average particle size was 165 ± 170 nm. Near-infrared (NIR) irradiation assays (810 nm, 0.1 W/cm2, 30 min, 180 J/cm2) confirmed that MoS2 nanosheets can efficiently convert NIR light into heat and reach 52 °C. The therapeutic doses of MoS2 (125 µg/mL) and Tegafur (50 µg/mL) were optimized and both were simultaneously incorporated into a Carbopol hydrogel. The cells were brought into contact with the hydrogel and irradiated with a custom-built NIR LED system. In HFF-1 cells (normal human fibroblasts), the metabolic activity was 78% (above the 70% toxicity limit—ISO 10993-5:2009(E)), while in A-431 skin cancer cells, it was 28%. In addition, the MoS2 + Tegafur hydrogels led to a 1.9-fold decrease in A-431 cancer cell metabolic activity, 72 h after irradiation, in comparison to MoS2 hydrogels, indicating a combined effect of photothermal and chemotherapy. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma (BCC) is the most common form of human cancer, and treatment usually involves surgery, with alternative strategies being needed. We propose the use of carbopol hydrogels (HG) for topical administration of nanographene oxide (GOn) and partially-reduced nanographene oxide (p-rGOn) for photothermal therapy (PTT) of BCC. GOn and p-rGOn incorporated into the HG present lateral sizes ∼200 nm, being stable for 8 months. After 20 min irradiation with an infrared (IR) photothermal therapy lamp (15.70 mW cm -2 ), GOn-HG increased temperature to 44.7 °C, while p-rGOn-HG reached 47.0 °C. Human skin fibroblasts (HFF-1) cultured with both hydrogels (250 μg mL -1 ) maintained their morphology and viability. After 20 min IR irradiation, p-rGOn HG (250 μg mL -1 ) completely eradicated skin cancer cells (A-431). Ex vivo human skin permeability tests showed that the materials can successfully achieve therapeutic concentrations (250 μg mL -1 ) inside the skin, in 2.0 h for GO HG or 0.5 h for p-rGOn HG., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

The main challenges associated to the application of graphene-based materials (GBM) in phototherapy are obtaining particles with lateral nanoscale dimensions and water stability that present high near-infrared (NIR) absorption. Nanosized graphene oxide (GOn) is stable in aqueous dispersion, due to the oxygen functionalities on its surface, but possesses low photothermal efficiency in NIR region. GOn total reduction originates reduced nanographene oxide (rGOn) that presents high NIR absorption, but poor water stability. In this work, we produced a partially reduced nanographene oxide (p-rGOn) by GOn photoreduction using ultraviolet radiation (UV-C), yielding nanometric particles that preserve the original water stability, but acquire high light-to-heat conversion efficiency. GOn and p-rGOn presented mean particle sizes of 170 ± 81 nm and 188 ± 99 nm, respectively. 8 h of UV-C irradiation allowed to obtain a p-rGOn stable for up 6 months in water, with a zeta potential of -32.3 ± 1.3 mV. p-rGOn water dispersions have shown to absorb NIR radiation, reaching 52.7 °C (250 µg mL -1 ) after 30 min NIR irradiation. Chemical characterization of p-rGOn showed a decrease in the number of characteristic oxygen functional groups, confirming GOn partial reduction. Furthermore, p-rGOn (250 µg mL -1 ) didn't cause any cytotoxicity (ISO10993-5:2009(E)) towards human skin fibroblasts (HFF-1) and human skin keratinocytes (HaCat), after 24 and 48 h incubation. An innovative custom-built NIR LED-system has been developed and validated for p-rGOn photothermal effect evaluation. Finally, exposure to p-rGOn+NIR-LEDs has caused no cytotoxicity towards HFF-1 or HaCat cells, revealing its potential to be used as a safe therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)