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Published on: October 28, 2015
Pharmaceutical Formulations Containing Graphene and 5-Fluorouracil for Light-Emitting Diode-Based Photochemotherapy
Sara I Amaral1,2,3,4, Filipa A L S Silva1,2,3,4, Raquel Costa-Almeida3,4
1LEPABE─Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculdade de Engenharia, Universidade do Porto, Rua Dr. Roberto Frias s/n, 4200-180 Porto, Portugal.
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.
Insights
Partially reduced nanographene oxide (p-rGOn) in a hydrogel combined photothermal therapy and chemotherapy for basal cell carcinoma. This novel graphene-based formulation demonstrated significant cancer cell eradication with minimal toxicity to normal skin cells.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Dermatology
Background:
- Nonmelanoma skin cancer (NMSC), primarily basal cell carcinoma (BCC), is the most common cancer globally.
- Existing therapies for BCC often suffer from low efficacy, adverse effects, and high recurrence rates, necessitating novel treatment strategies.
- Graphene-based nanomaterials offer unique properties for biomedical applications, including photothermal conversion.
Purpose of the Study:
- To develop and evaluate a novel graphene-based hydrogel formulation for combined photothermal therapy (PTT) and chemotherapy against basal cell carcinoma (BCC).
- To assess the efficacy and safety of the developed formulation using in vitro models of skin cancer.
- To explore the potential of partially reduced nanographene oxide (p-rGOn) as a photosensitizer for PTT in BCC treatment.
Main Methods:
- Synthesis of partially reduced nanographene oxide (p-rGOn) nanoparticles via controlled UV-C reduction of nanographene oxide.
- Incorporation of p-rGOn and the chemotherapeutic agent 5-fluorouracil (5-FU) into a Carbopol hydrogel matrix.
- In vitro evaluation of cytotoxicity on normal skin cells (HFF-1) and efficacy against A-431 skin cancer cells under near-infrared (NIR) irradiation using a custom-developed LED system.
Main Results:
- The synthesized p-rGOn particles were sub-200 nm, water-stable, and exhibited high light-to-heat conversion efficiency.
- Carbopol/p-rGOn/5-FU hydrogels showed no cytotoxicity towards normal HFF-1 skin cells.
- Exposure of A-431 skin cancer cells to NIR irradiation with the hydrogel resulted in a 90% reduction in cell number and 80% cell death after 72 hours, indicating significant therapeutic efficacy.
- The study highlights the potential of a tailored LED system for safe and selective phototherapy delivery.
Conclusions:
- The developed Carbopol/p-rGOn/5-FU hydrogel represents a promising new platform for combined PTT and chemotherapy in BCC treatment.
- This graphene-based formulation offers a potentially safer and more effective alternative to conventional BCC therapies.
- These findings constitute the first report on graphene-based pharmaceutical formulations for BCC phototherapy.
