Targeted photosensitizer nanoconjugates based on human serum albumin selectively kill tumor cells upon photo-irradiation

Abstract

A photosensitizer (Chlorin e6, Ce6) nanoconjugate based on human serum albumin (HSA) was designed and prepared for tumor cell targeted photodynamic therapy. The resulting nanoconjugates consisted of multiple cyclic Arg–Gly–Asp–D-Tyr–Cys peptides (cRGD) and about 5.4 Ce6 on each HSA molecule (RGD–HSA–Ce6). RGD–HSA–Ce6 exhibited small size with a mean diameter of 31.1 nm and negative charge with −15.9 mV. Due to the incorporation of targeting moiety, RGD–HSA–Ce6 could be specifically recognized by αvβ3 integrin overexpressed tumor cells, as well as internalized into late endosomes and lysosomes efficiently. In addition, RGD–HSA–Ce6 exhibited low dark toxicity in both tumor and normal cell lines. Upon photo-irradiation, RGD–HSA–Ce6 exhibited high phototoxicity against αvβ3 integrin overexpressed A375 melanoma cells, indicating the considerable potential for effective photodynamic therapy. Combined with the low phototoxicity to normal fibroblast 3T3 cells, RGD–HSA–Ce6 developed in this study may provide an effective tool for targeted photodynamic therapy to tumor cells.