Study On Fullerene (C60) Nanomaterial Based Tumor Photodynamic Therapy

Photodynamic therapy (PDT) has lower potential for peripheral toxicity than many conventional cancer therapies and has become an increasingly recognized alternative for traditional therapies in the clinic, the photosensitizer is one of important components for PDT. The properties of an ideal photosensitizer are water solubility, low cytotoxicity in the dark, high ability to produce reactive oxygen species(ROS). Fullerenes possess unique photophysical properties:under the inuence of UV or visible light irradiation, C60 molecule is able to shift to the exitation triplet state and generate singlet and other active forms of oxygen, Such characteristics of fullerenes are evidenced on their potential use in photosensitizer. However, fullerenes themselves are insoluble in water and polar solvents. The low solubility of fullerenes in the water limits their use in biological studies. The characteristics of water-soluble C60 nanoparticles as a photosensitizer against cancer cells and increased intra cellular reactive oxygen species were evaluated. Take C60 and clinical treatments of photosensitizer into one system, could achieve nano drug-dilivery system, in order to improve PDT protocol for cancer control. Sustained released C60 implants was developed to get a system for combination chemotherapy with PDT.1 Investigation of C60 amino acid nanoparticles and its photodynamic therapy The propensity of fullerene for adding various reagents with formation could be exploited, due to the π-conjugated structure of C60. Fullerene amino acids nanoparticles have been prepared by chemical conjugation of amino acid to C60. C60 modied with l-phenylalanine (C60-phe) or glycine (C60-gly) was very effcient to carry out photodynamic activity leading to cleavage of plasmid DNA in vitro. These C60 amino acid nanoparticles were the most active photosensitizer against SGC-7901 cells, MCF-7 cells SMMC-7721 cells and PC3 cells; induced cancer cells apoptosis after illumination; caused a perturbation of the cell cycle. It produced diffuse intracellular fluorescence when DCFH-DA was added as an ROS probe, suggesting phototoxicity of these derivatives related with the generation of intracellular ROS. These nanoparticle solutions up regulated the expression of phosphorylated (p)p38MAPK. NAC significantly depressed the composite induced activation of p38MAPK, and the kinase inhibitor SB203580 significantly prevented C60 derivative-induced cell apoptosis.This study revealed that p38MAPK is activated by C60 nanoparticles through ROS generation,leading to cancer cell injuries.25-Aminolevulinic acid-loaded fullerene nanoparticles for in vitro and in vivo photodynamic therapyIn order to improve the penetration of 5-ALA through the natural barriers, and the solubility of C60, Fullerene 5-ALA nanoparticles have been prepared by chemical conjugation of 5-ALA to C60.80-200 nm nanoparticles containing 5-aminolevulinic acid (ALA) and fullerene (C60) for photodynamic therapy. Compared with ALA, the nanoparticles yielded more protoporphytin (PpIX) formation in B16-F10 cells and tumor tissues, significantly improved in antitumor efficacy in tumor-bearing mice. Maximum levels of PpIX were obtained 4 h after administration and selective PpIX formation in tumor was observed. The product was superior to ALA alone in promoting PpIX biosynthesis and PDT efficacy both in culture cells and in a murine tumor model. PpIX level in tumor tissue was significantly higher than other organs (p<0.05).These results suggest that this procedure could be the basis for an improved PDT protocol for cancer control.3 Preparation and characterization of injectable Mitoxantrone Poly (lactic acid)/ Fullerene implants for in vivo chemo-photodynamic therapyC60 L-phenylalanine derivative attached with poly (lactic acid) (C60-phe-PLA) through ester bonds was developed to prepare injectable multifunctional implants. In this study, C60-phe-PLA was self-assembled to form microspheres consisting of a hydrophilic antitumor drug (MTX) and a hydrophobic block (C60) by dispersion-solvent diffusion method, orthogonal tests were used to optimize the prescriptions.The self-assembled microspheres showed sustained release pattern almost 15 days in vitro release experiments. Intratumoral administration of the microspheres, C57BL/6 mice did not cause rejection. According to the tissue distribution, MTX mainly distributed in tumors, and rarely in heart, liver, spleen, lung, and kidney. Microspheres with laser irradiation exhibited a good photodynamic activity, and photodynamic therapy combined with chemotherapy had a synergistic enhancement of tumor therapy, tumor volume was significantly decreased.