Targeting integrin-rich tumors with temoporfin-loaded vitamin-E-succinate-grafted chitosan oligosaccharide/D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles to enhance photodynamic therapy efficiency

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Abstract

A major challenge in cancer photodynamic therapy (PDT) is the poor 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) (c[RGDfK])-modified D-α-tocopheryl polyethylene glycol 1000 succinate, were prepared (RGD-NPs) and were expected to enhance the accumulation of mTHPC in integrin-rich U87MG tumors. The RGD-NPs generated were 144.9 nm in diameter and uniformly spherical. After irradiation, RGD-NPs effectively generated singlet oxygen, and displayed enhanced cellular uptake and cytotoxicity in U87MG cells. 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. 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.

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