Study On MTHPC Loaded VES-g-CSO/TPGS-RGD Nanoparticle Delivery System For Photodynamic Therapy Of Tumor

The major challenges in tumor photodynamic therapy(PDT)are the poor solubility and tumor selectivity of the photosensitizer.Therefore,temoporfin(mTHPC)-loaded nanoparticles,based on vitamin-E-succinate-grafted chitosan oligosaccharide and cyclic(arginine-glycine-aspartic acid-D-phenylalanine-lysine)-modified D-?-tocopheryl polyethylene glycol 1000 succinate,were prepared(RGD-NPs)and expected to enhance the accumulation of mTHPC in integrin-rich U87MG tumors.The physical characteristics and antitumor effects of mTHPC loaded nanoparticles were investigated in vivo and in vitro,which provided a theoretical basis for further research and development of RGD-NPs for photodynamic therapy of cancer.mTHPC-loaded VES-g-CSO/TPGS nanoparticles(NPs)and mTHPC-loaded VES-g-CSO/TPGS-RGD nanoparticles(RGD-NPs)were prepared with a modified cosolvent evaporation method.The RGD-NPs generated were 144.9 ± 4.11 nm in diameter and zeta potential were 33.3 ±2.10 mV,TEM and AFM analysis of RGD-NPs showed spherical particles.The LC%values were 1.98± 0.12%for NPs and 2.24 ± 0.10%for RGD-NPs,respectively.NPs and RGD-NPs show similar sustained release.DPBF was used to assess the levels of singlet oxygen generated,the ?? values for RGD-NPs was 0.36,which were slightly lower than that for Free mTHPC(0.43).The generation of singlet oxygen was also detected at the cellular level as the fluorescence of oxidized DCFH-DA.RGD-NPs effectively generated singlet oxygen indicated that the mTHPC encapsulated in the nanoparticles effectively produced singlet oxygen,which is consistent with the results for the quantum yields of singlet oxygen.The intracellular localization of RGD-NPs in U87MG cells was determined with CLSM.The cells incubated with RGD-NPs showed the strongest red fluorescence.An MTT assay was used to evaluate the cytotoxicity of RGD-NPs,the IC50 values were 8.35 ?g/mL for Free mTHPC,3.11 ?g/mL for NPs,and 0.27 ?g/mL for RGD-NPs,RGD-NPs exerted the strongest cytotoxicity.A quantitative analysis of apoptotic efficiency showed that when laser treatment was included,RGD-NPs have higher apoptosis induction activity than NPs in U87MG cells.What's more,the RGD-NPs also penetrated deep into U87MG tumor spheroids,with a tumor-targeting ability and antitumor efficacy superior to those of unmodified nanoparticles in subcutaneous-tumor-bearing nude mice.Near-infrared imaging was used to evaluate the targeting effect of RGD-NPs in subcutaneous-tumor-bearing nude mice.Results showed that the accumulation of RGD-NPs in the tumors was much greater than the accumulation of nonspecific NPs.The inhibitory effect of the mTHPC-loaded nanoparticles on tumor growth in vivo is consistent with the results for U87MG tumor spheroids.A histopathological analysis confirmed the increased anticancer efficacy of RGD-NPs,with less systemic toxicity than unmodified nanoparticles.Therefore,the RGD-NPs developed in this study potentially target integrin-rich tumors and enhance the efficiency of PDT.