Treatment of breast cancer with autophagy inhibitory microRNAs carried by AGO2-conjugated nanoparticles

摘要: Nanoparticle based gene delivery systems holds great promise. Superparamagnetic iron oxide nanoparticles (SPIONs) are being heavily investigated due to good biocompatibility and added diagnostic potential, rendering such theranostic. Yet, commonly used cationic coatings for efficient of anionic cargos, results in significant toxicity limiting translation the technology clinic. Here, we describe a highly biocompatible, small non-cationic SPION-based theranostic as novel therapy agents. We propose first-time, usage microRNA machinery RISC complex component Argonaute 2 (AGO2) protein stabilizing agent vehicle. In this study, AGO2 protein-conjugated, anti-HER2 antibody-linked fluorophore-tagged SPION were developed (SP-AH nanoparticles) carrier an autophagy inhibitory microRNA, MIR376B. These functionalized selectively delivered effective amount into HER2-positive breast cancer cell lines vitro xenograft nude mice model vivo, successfully blocked autophagy. Furthermore, combination chemotherapy cisplatin with MIR376B-loaded SP-AH increased efficacy anti-cancer treatment both cells vivo mice. Therefore, that conjugated SPIONs new class can be efficiently innovative, non-cationic, non-toxic tools targeted cancer.