Bio responsive self-assembly of Au-miRNAs for targeted cancer theranostics

Background: MicroRNA (miRNA) therapeutics are a promising approach to cancer treatment. However, this method faces considerable challenges to achieve tissue-specific, efficient, and safe delivery of miRNAs in vivo. Methods: Herein, we developed a miRNA delivery system based on the in situ self-assembly of Au-miRNA nanocomplexes (Au-miRNA NCs). Within the cancer microenvironment, we constructed in situ self-assembled Au-miRNA NCs by coincubating gold salt and tumor suppressor mimics, such as let-7a, miRNA-34a, and miRNA-200a. Findings: The in vitro experiments demonstrated that characteristic in situ self-assembled Au-miRNA NCs were present in cancer cells and can be taken up to inhibit the proliferation of cancer cells effectively. Most importantly, as proven in subcutaneous tumor treatment models, Au-miRNA NCs were especially useful for accurate target imaging and tumor suppression, with significantly enhanced antitumor effects for combination therapy. Interpretation: These observations highlight that a new strategy for the in situ biosynthesis of Au-let-7a NCs, Au-miR-34a NCs, and Au-miR-200a NCs is feasible, and this may assist in the delivery of more miRNA to tumor cells for cancer treatment. This work opens up new opportunities for the development of miRNA tumor therapy strategies. Funding: National Natural Science Foundation of China (91753106); Primary Research & Development Plan of Jiangsu Province (BE2019716); National Key Research and Development Program of China (2017YFA0205300). Keywords: Nano-complexes, microRNA delivery, In situ self-assembly, Tumor microenvironment, Cancer treatment