Drug resistance is an important reason to the treatment failure of cancer chemotherapy. In this paper, an amphiphilic tumor-targeting chimeric peptide-based drug self-delivery system (DSDS) was designed to overcome drug resistance by synergistic chemo-photodynamic therapy. Doxorubicin (Dox) was encapsulated into the micelles formed by the self-assembly of protoporphyrin IX (PpIX) derivated amphiphilic chimeric peptides (PpIX-PEG8-PEG8-RGDS) with high loading capacities of 25.85% for DOX and 29.49% for PpIX. The RGDS peptide moiety promoted the cell internalization of micelles by αυβ3 integrin-overexpressed cancer cells. Upon given 630 nm light irradiation, cytotoxic reactive oxygen species (ROS) were generated from PpIX to destroy the lysosomes and help release the micelles, which further underwent efficient therapeutic effect to MCF-7/ADR cells. The micelles undergo photodynamic therapy while slowly release DOX in lysosomes, preventing DOX from being pumped out the cell by P-glycoprotein. The nanomicellar drug self-delivery system proposed in this work exhibited significantly synergistic chemo-photodynamic therapy and provided a new platform for the therapy of drug resistant tumor cells.

中文翻译：

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两亲性肿瘤靶向嵌合肽基药物自递送纳米胶束通过协同化学光动力疗法克服癌症耐药性

耐药性是癌症化疗治疗失败的重要原因。在本文中，设计了一种基于两亲性肿瘤靶向嵌合肽的药物自递送系统（DSDS），以通过协同化学光动力疗法克服耐药性。多柔比星 (Dox) 被封装到由原卟啉 IX (PpIX) 衍生的两亲性嵌合肽 (PpIX-PEG8-PEG8-RGDS) 自组装形成的胶束中，DOX 的负载能力为 25.85%，PpIX 的负载能力为 29.49%。RGDS 肽部分通过 αυβ3 整合素过表达的癌细胞促进胶束的细胞内化。在给予 630 nm 光照射后，PpIX 产生细胞毒性活性氧 (ROS) 以破坏溶酶体并帮助释放胶束，从而进一步对 MCF-7/ADR 细胞产生有效的治疗效果。胶束经过光动力治疗，同时在溶酶体中缓慢释放 DOX，防止 DOX 被 P-糖蛋白泵出细胞。该工作提出的纳米胶束药物自递送系统表现出显着的协同化学光动力疗法，为耐药肿瘤细胞的治疗提供了新的平台。