Issue

Vol. 11 (2019)

Drug Nanorod-Mediated Intracellular Delivery of microRNA-101 for Self-sensitization via Autophagy Inhibition

https://doi.org/10.1007/s40820-019-0310-0
Xiaofei Xin
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, People’s Republic of China
Xiaoqing Du
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, People’s Republic of China
Qingqing Xiao
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, People’s Republic of China
Helena S. Azevedo
School of Engineering and Materials Science, Institute of Bioengineering, Queen Mary, University of London, London E1 4NS, UK
Wei He
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, People’s Republic of China
Lifang Yin
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, People’s Republic of China

Corresponding Author: Lifang Yin

1019940752@cpu.edu.cn

Nano-Micro Letters, Vol. 11 (2019), Article Number: 82

Abstract

Autophagy is closely related to the drug resistance and metastasis in cancer therapy. Nanoparticle-mediated co-delivery of combinatorial therapy with small-molecular drugs and nucleic acids is promising to address drug resistance. Here, a drug-delivering-drug (DDD) platform consisting of anti-tumor-drug nanorods as a vehicle for cytosol delivery of nucleic acid (miR-101) with potent autophagic-inhibition activity is reported for combinatorial therapy. The developed 180-nm nanoplatform, with total drug loading of up to 66%, delivers miR-101 to cancer cells, with threefold increase in intracellular level compared to conventional gene carriers and inhibits the autophagy significantly, along with above twofold reduction in LC3II mRNA and approximately fivefold increase in p62 mRNA over the control demonstrated in the results in vivo. And in turn, the delivery of miR-101 potentiates the drug’s ability to kill cancer cells, with a threefold increase in apoptosis over that of chemotherapy alone. The anti-tumor study in vivo indicates the combined therapy that enables a reduction of 80% in tumor volume and > twofold increase in apoptosis than of the single-drug strategy. In summary, via the carrier-free strategy of DDD, this work provides a delivery platform that can be easily customized to overcome drug resistance and facilitates the delivery of combined therapy of small-molecular drugs and nucleic acids.


Highlights:


1 Nanosized cytotoxic drug could combat against the autophagy induced by the drug.
2 The drug nanorods enabled efficient intracellular delivery of the nucleic acid and the resultant autophagy inhibition in vitro and in vivo, which in turn sensitized the cancer cells to the anti-tumor nanorods.

Keywords

Nanocrystals MicroRNA delivery Autophagy inhibition Cytotoxicity Combinatorial therapy
Xin, Xiaofei, Xiaoqing Du, Qingqing Xiao, Helena S. Azevedo, Wei He, and Lifang Yin. 2019. “Drug Nanorod-Mediated Intracellular Delivery of MicroRNA-101 for Self-Sensitization via Autophagy Inhibition”. Nano-Micro Letters 11 (September):82. https://doi.org/10.1007/s40820-019-0310-0.
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