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

机译:基于人血清白蛋白的靶向光敏剂纳米共轭物在光照射下选择性杀死肿瘤细胞

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摘要

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 alpha v beta 3 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 avb3 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.
机译:设计并制备了基于人血清白蛋白(HSA)的光敏剂(Chlorin e6,Ce6)纳米偶联物,用于靶向肿瘤细胞的光动力疗法。所得的纳米缀合物由多个环状Arg-Gly-Asp-D-Tyr-Cys肽(cRGD)和每个HSA分子(RGD-HSA-Ce6)上约5.4 Ce6组成。 RGD-HSA-Ce6的体积很小,平均直径为31.1 nm,负电荷为-15.9 mV。由于掺入了靶向部分,RGD-HSA-Ce6可以被αvbeta 3整联蛋白过表达的肿瘤细胞特异性识别,并有效地内化到晚期内体和溶酶体中。另外,RGD-HSA-Ce6在肿瘤细胞和正常细胞系中均显示出低的暗毒性。光照射后,RGD-HSA-Ce6对过表达avb3整联蛋白的A375黑色素瘤细胞表现出很高的光毒性,表明有效光动力疗法的巨大潜力。结合对正常成纤维细胞3T3细胞的低光毒性,本研究开发的RGD-HSA-Ce6可能为针对肿瘤细胞的靶向光动力治疗提供有效的工具。

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