Macrophages-Cancer Membrane-Encapsulated Metal-Organic Frameworks with Copper-Depleting Moiety for Mitochondria-Targeted Therapeutics.

Abstract

Mitochondria-targeted therapeutics are an attractive approach against energy-dependent cancer. However, effective mitochondria organelle therapeutics agents are still highly desirable. Herein, a mitochondria-targeted therapeutics platform, termed CDM@MUiO-DP@MCHM, consisting of macrophages-cancer hybrid membrane (MCHM) encapsulated MUiO-66 metal-organic frameworks (MOFs) is reported, which is loaded with microRNA (miRNA) biomarker detection probe (DP) for cancer diagnosis and copper-depleting moiety (CDM) for mitochondrial copper depletion to suppress cancer growth. Using nude mice bearing MCF-7 as model, after injecting intravenously via the caudal vein of mice, the encapsulation of MCHM can not only greatly enhance the cancer homing-targeting ability of the nanoparticles (NPs) but also endows the NPs the immune escape capacity to extend the circulation time. The miRNA-21 biomarker can be detected by the fluorescence signal for diagnosis, while the CDM induced energy deficiency and compromised mitochondria membrane potential, leading to apoptosis of the cancer cell. The good performance of CDM@MUiO-DP@MCHM suggest the great potential mitochondria organelle therapeutics.