State Key Laboratory of Bioelectronics (Chien-Shiung Wu Lab), School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China; Shunde Hospital of Southern Medical University, Shunde 528300, China.
State Key Laboratory of Bioelectronics (Chien-Shiung Wu Lab), School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.
EBioMedicine. 2020 Apr;54:102740. doi: 10.1016/j.ebiom.2020.102740. Epub 2020 Apr 7.
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.
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.
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.
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.
National Natural Science Foundation of China (91753106); Primary Research & Development Plan of Jiangsu Province (BE2019716); National Key Research and Development Program of China (2017YFA0205300).
微小 RNA（miRNA）治疗是癌症治疗的一种很有前途的方法。然而，这种方法在实现 miRNA 在体内的组织特异性、高效和安全递送上面临着相当大的挑战。
本文中，我们开发了一种基于 Au-miRNA 纳米复合物（Au-miRNA NCs）原位自组装的 miRNA 递药系统。在癌症微环境中，我们通过共孵育金盐和肿瘤抑制模拟物（如 let-7a、miRNA-34a 和 miRNA-200a）构建了原位自组装的 Au-miRNA NCs。
体外实验表明，特征性的原位自组装的 Au-miRNA NCs 存在于癌细胞中，并能被有效摄取以抑制癌细胞的增殖。最重要的是，正如皮下肿瘤治疗模型所证明的那样，Au-miRNA NCs 特别有助于精确的肿瘤靶向成像和抑制，联合治疗的抗肿瘤效果显著增强。
这些观察结果强调了原位生物合成 Au-let-7a NCs、Au-miR-34a NCs 和 Au-miR-200a NCs 的新策略是可行的，这可能有助于将更多的 miRNA 递送到肿瘤细胞中用于癌症治疗。这项工作为 miRNA 肿瘤治疗策略的发展开辟了新的机会。
国家自然科学基金（91753106）；江苏省基础研究计划（BE2019716）；国家重点研发计划（2017YFA0205300）。
