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