Functionalized Fullerenes in Photodynamic Therapy

Abstract

Since the discovery of C60 fullerene in 1985, scientists have been searching for biomedical applications of this most fascinating of molecules. The unique photophysical and photochemical properties of C60 suggested that the molecule would function well as a photosensitizer in photodynamic therapy (PDT). PDT uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that kill unwanted cells. However the extreme insolubility and hydrophobicity of pristine C60, mandated that the cage be functionalized with chemical groups that provided water solubility and biological targeting ability. It has been found that cationic quaternary ammonium groups provide both these features, and this review covers work on the use of cationic fullerenes to mediate destruction of cancer cells and pathogenic microorganisms in vitro and describes the treatment of tumors and microbial infections in mouse models. The design, synthesis, and use of simple pyrrolidinium salts, more complex decacationic chains, and light-harvesting antennae that can be attached to C60, C70 and C84 cages are covered. In the case of bacterial wound infections mice can be saved from certain death by fullerene-mediated PDT.

Can Nanotechnology Shine a New Light on Antimicrobial Photodynamic Therapies?

“…Fullerenes (C60) are the third type of carbon structure; they consist of 60 carbon atoms arranged in a spherical structure that can absorb light and be active PS [62], they generate different ROS according to the solvent, and in polar solvents they produce superoxide and hydroxyl radicals, while in nonpolar solvents they predominantly generate singlet oxygen. As shown from recent studies, their functionalization (with multiple attached cationic groups) make them more soluble in water or other biological fluids and more active for targeting and killing different bacterial species [63]. Titanium oxide (TiO 2 ) has been more widely studied as a PS among metal oxide nanoparticles in a process termed "photocatalysis," which has been proposed as an antimicrobial strategy for disinfection of surfaces, air, and water [64,65].…”

Antibacterial photodynamic therapy: overview of a promising approach to fight antibiotic-resistant bacterial infections

“…Spheroidal fullerenes such as C60 [59] and C70 [60] (Table 1) are football-like structures composed of pentagonal and hexagonal rings that can absorb visible light [61] and mediate photochemical reactions from the excited state [60,[62][63][64]. The photo-excited fullerenes can react with electron donors to generate fullerene radical anions (C60…”

“…Due to the highly lipophilic and non-charged structure, native fullerenes exhibit poor PS-bacterial cell association and are therefore relatively inactive as PSs against bacteria [64,74]. Fullerenes must be chemically modified with amphiphilic molecules [75] to enable bacterial photosensitization.…”

“…Finally, fullerene derivatives are more stable than tetrapyrrole-based PSs such as porphyrins and chlorins [74], which may render these PSs more suitable for pharmacological formulations and clinical use. A dedicated review on fullerenes as potent PSs in PDT and APDT is available elsewhere [64].…”

“…The PSs that have been tested in vivo include phenothiaziniums (section 2.1) such as methylene blue [19,209], Rose Bengal [210], and EtNBS [188] (Table 1), ZnPc derivative RLP068/Cl [211], (Table 1), and C70 fullerene [60,64,68] (Table 1), among others. Animal models have been developed that mimic clinical infections, including a mouse model of skin abrasion caused by MRSA [212] and a guinea pig model of burn infections with S. aureus [213].…”