Department of Pharmaceutical Engineering, College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan 410083, P. R. China.
Department of Pharmaceutics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, P. R. China.
Mol Pharm. 2022 Mar 7;19(3):805-818. doi: 10.1021/acs.molpharmaceut.1c00720. Epub 2022 Feb 11.
Biomimetic therapeutics offer great potential for drug delivery that avoids immune recognition. However, the coated cell membrane usually hinders the cellular uptake of nanoparticles; thus, structure-changeable formulations have attracted increasing attention. Herein, we report photolytic pyropheophorbide a (PA)-inserted red blood cell (RBC) membrane-camouflaged curcumin dimeric prodrug (CUR-TK)-poly(lactic--glycolic acid) (PLGA) nanoparticles [(CUR-TK)-PLGA@RBC-PA] for enhanced cancer therapy. In these nanoparticles, the inner core was constructed using PLGA and loaded with our synthesized reactive oxygen species (ROS)-responsive cleavable curcumin dimeric prodrug (CUR-TK). The nanoparticles generated ROS in response to the light irradiation attributed to the incorporated PA. The ROS further triggered the lysis of the cell membrane and exposed the nanoparticles for enhanced tumor cellular uptake, and the ROS also cleaved CUR-TK for controlled CUR drug release. Moreover, the ROS performed photodynamic therapy (PDT). The chemotherapy and PDT produced a combined effect in the treatment of cancer cells, thus enhancing anticancer therapeutic efficacy.
仿生治疗学为避免免疫识别的药物输送提供了巨大的潜力。然而，涂层细胞膜通常会阻碍纳米颗粒的细胞摄取；因此，结构可变形制剂引起了越来越多的关注。在此，我们报告了光解叶绿酸 a（PA）插入的红细胞（RBC）膜伪装姜黄素二聚体前药（CUR-TK）-聚（乳酸-乙醇酸）（PLGA）纳米粒子[（CUR-TK）-PLGA@RBC-PA]，用于增强癌症治疗。在这些纳米粒子中，内核由 PLGA 构建，并负载有我们合成的活性氧（ROS）响应性可裂解姜黄素二聚体前药（CUR-TK）。纳米粒子在光照射下产生 ROS，这归因于掺入的 PA。ROS 进一步触发细胞膜裂解，暴露纳米颗粒以增强肿瘤细胞摄取，ROS 还裂解 CUR-TK 以控制 CUR 药物释放。此外，ROS 进行光动力治疗（PDT）。化疗和 PDT 在治疗癌细胞时产生协同作用，从而增强了抗癌治疗效果。
