MiRNA Delivery System Based on Stimuli-Responsive Gold Nanoparticle Aggregates for Multimodal Tumor Therapy

Abstract

In this work, a composite of microRNA-124-5p mimics (miR-124-5p) and gold nanoparticle (AuNP) aggregates was fabricated to combine the gene therapy and photothermal therapy for effective tumor medicine. The AuNP aggregates cross-linked by cystamine not only serve as photothermal therapeutic agents but are able to condense miR-124-5p as nanocarrier for gene delivery because of the coulomb interaction. The release of miR-124-5p could be initiated by the cleavage of cystamine when the nanocarrier enter the cytoplasm of tumor cells through endocytosis, where contains high concentration of glutathione (GSH). Moreover, the size of the AuNP aggregates did not change after the GSH-triggered miR-124-5p release because of the coinstantaneous disruption of disulfide bond and reformation of the thiol-gold bond, resulting in sustained photothermal property of the nanocarrier for tumor therapy. In vitro experiments showed that the miRNA@AuNAs (miR-124-5p) composite under near-infrared radiation performed great cytotoxicity to tumor cells, which is two and three times higher than the group of pure AuNP aggregates under near-infrared radiation and miRNA@AuNAs composite without near-infrared radiation, respectively. All experiment statistics show that the miRNA@AuNAs composite with combination of photothermal therapy and gene therapy has great potential for effective tumor treatment.