Department of Blood Transfusion, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P. R. China.
Department of Orthopedics, Changsha Hospital of Traditional Chinese Medicine, Changsha Eighth Hospital, Changsha, Hunan 410013, P. R. China.
Mol Pharm. 2024 Jul 1;21(7):3577-3590. doi: 10.1021/acs.molpharmaceut.4c00307. Epub 2024 Jun 10.
Triple-negative breast cancer (TNBC) is characterized by high malignancy and limited treatment options. Given the pressing need for more effective treatments for TNBC, this study aimed to develop platelet membrane (PM)-camouflaged silver metal-organic framework nanoparticles (PM@MOF-Ag NPs), a biomimetic nanodrug. PM@MOF-Ag NP construction involved the utilization of 2-methylimidazole and silver nitrate to prepare silver metal-organic framework (MOF-Ag) NPs. The PM@MOF-Ag NPs, due to their camouflage, possess excellent blood compatibility, immune escape ability, and a strong affinity for 4T1 tumor cells. This enhances their circulation time in vivo and promotes the aggregation of PM@MOF-Ag NPs at the 4T1 tumor site. Importantly, PM@MOF-Ag NPs demonstrated promising antitumor activity in vitro and in vivo. We further revealed that PM@MOF-Ag NPs induced tumor cell death by overproducing reactive oxygen species and promoting cell apoptosis. Moreover, PM@MOF-Ag NPs enhanced apoptosis by upregulating the ratios of Bax/Bcl-2 and cleaved caspase3/pro-caspase3. Notably, PM@MOF-Ag NPs exhibited no significant organ toxicity, whereas the administration of MOF-Ag NPs resulted in liver inflammation compared to the control group.
三阴性乳腺癌(TNBC)具有高度恶性和有限的治疗选择。鉴于迫切需要更有效的 TNBC 治疗方法,本研究旨在开发血小板膜(PM)伪装的银金属有机骨架纳米粒子(PM@MOF-Ag NPs),这是一种仿生纳米药物。PM@MOF-Ag NP 的构建涉及使用 2-甲基咪唑和硝酸银来制备银金属有机骨架(MOF-Ag) NPs。PM@MOF-Ag NPs 由于其伪装,具有出色的血液相容性、免疫逃逸能力和对 4T1 肿瘤细胞的强烈亲和力。这增强了它们在体内的循环时间,并促进了 PM@MOF-Ag NPs 在 4T1 肿瘤部位的聚集。重要的是,PM@MOF-Ag NPs 在体外和体内均显示出有前途的抗肿瘤活性。我们进一步揭示,PM@MOF-Ag NPs 通过过度产生活性氧和促进细胞凋亡来诱导肿瘤细胞死亡。此外,PM@MOF-Ag NPs 通过上调 Bax/Bcl-2 和 cleaved caspase3/pro-caspase3 的比值来增强凋亡。值得注意的是,PM@MOF-Ag NPs 没有表现出明显的器官毒性,而与对照组相比,MOF-Ag NPs 的给药导致肝脏炎症。
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