聚合物囊泡共递送多柔比星和蜂毒素以克服多药耐药性的研究进展。
Development of Polymersomes Co-Delivering Doxorubicin and Melittin to Overcome Multidrug Resistance.
机构信息
Department of Chemical and Biomolecular Engineering, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea.
Department of Life Science, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea.
出版信息
Molecules. 2023 Jan 21;28(3):1087. doi: 10.3390/molecules28031087.
Multidrug resistance (MDR) is one of the major barriers in chemotherapy. It is often related to the overexpression of efflux receptors such as P-glycoprotein (P-gp). Overexpressed efflux receptors inhibit chemotherapeutic efficacy by pumping out intracellularly delivered anticancer drugs. In P-gp-mediated MDR-related pathways, PI3K/Akt and NF-kB pathways are commonly activated signaling pathways, but these pathways are downregulated by melittin, a main component of bee venom. In this study, a polymersome based on a poly (lactic acid) (PLA)-hyaluronic acid (HA) (20k-10k) di-block copolymer and encapsulating melittin and doxorubicin was developed to overcome anticancer resistance and enhance chemotherapeutic efficacy. Through the simultaneous delivery of doxorubicin and melittin, PI3K/Akt and NF-κB pathways could be effectively inhibited, thereby downregulating P-gp and successfully enhancing chemotherapeutic efficacy. In conclusion, a polymersome carrying an anticancer drug and melittin could overcome MDR by regulating P-gp overexpression pathways.
多药耐药性（MDR）是化疗的主要障碍之一。它通常与外排受体（如 P-糖蛋白（P-gp））的过度表达有关。过度表达的外排受体通过泵出细胞内递送的抗癌药物来抑制化疗效果。在 P-gp 介导的 MDR 相关途径中，PI3K/Akt 和 NF-κB 途径是常见的激活信号通路，但这些通路被蜂毒的主要成分蜂肽下调。在这项研究中，开发了一种基于聚（乳酸）（PLA）-透明质酸（HA）（20k-10k）二嵌段共聚物的聚合物囊，该聚合物囊包封了蜂肽和阿霉素，以克服抗癌耐药性并增强化疗效果。通过同时递送阿霉素和蜂肽，可以有效抑制 PI3K/Akt 和 NF-κB 途径，从而下调 P-gp，并成功增强化疗效果。总之，载有抗癌药物和蜂肽的聚合物囊可以通过调节 P-gp 过度表达途径来克服 MDR。
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