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肿瘤靶向联合治疗系统,用于有效治疗耐药性三阴性乳腺癌。

Tumor targeted combination therapeutic system for the effective treatment of drug resistant triple negative breast cancer.

机构信息

Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.

Key Laboratory of Pharmacology of the State Administration of Traditional Chinese Medicine, Xi'an 710032, China; Department of Chemistry, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.

出版信息

Int J Pharm. 2023 Apr 5;636:122821. doi: 10.1016/j.ijpharm.2023.122821. Epub 2023 Mar 11.

Abstract

Breast cancer has become the malignant tumor with the largest incidence, especially the drug resistant triple negative breast cancer (TNBC). The combination therapeutic system can play a better role in resisting drug resistant TNBC. In this study, dopamine and tumor targeted folic acid modified dopamine were synthesized as carrier materials to construct melanin-like tumor targeted combination therapeutic system. The optimized nanoparticles of CPT/Fe@PDA-FA10 with efficient loading of camptothecin and iron was achieved, which showed tumor targeted delivery ability, pH sensitive controlled release, effective photothermal conversion performance and excellent anti-tumor efficacy in vitro and in vivo. CPT/Fe@PDA-FA10 plus laser could significantly kill the drug resistant tumor cells, inhibit the growth of the orthotopic drug resistant triple negative breast cancer through apoptosis/ferroptosis/photothermal treatment, and had no significant side effects on the main tissues and organs. This strategy provided a new idea for the construction and clinical application of triple-combination therapeutic system as effective treatment for drug resistant triple negative breast cancer.

摘要

乳腺癌已成为发病率最高的恶性肿瘤,尤其是耐药性三阴性乳腺癌(TNBC)。联合治疗系统在抵抗耐药性 TNBC 方面可以发挥更好的作用。本研究以多巴胺和肿瘤靶向叶酸修饰的多巴胺为载体材料,构建了黑色素样肿瘤靶向联合治疗系统。优化了载有喜树碱和铁的 CPT/Fe@PDA-FA10 纳米粒,具有高效的载药能力、pH 敏感控制释放、有效的光热转换性能和优异的体外和体内抗肿瘤功效。CPT/Fe@PDA-FA10 联合激光治疗可以显著杀伤耐药肿瘤细胞,通过细胞凋亡/铁死亡/光热治疗抑制原位耐药三阴性乳腺癌的生长,对主要组织和器官无明显副作用。该策略为构建和临床应用三重联合治疗系统提供了新的思路,可作为治疗耐药性三阴性乳腺癌的有效方法。

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