15November2019

Nano-Micro Letters

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

Xiaofei Xin1, Xiaoqing Du1, Qingqing Xiao1, Helena S. Azevedo2, Wei He1, *, Lifang Yin1, *

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Nano-Micro Lett. (2019) 11: 82

First Online: 25 September 2019 (Article)

DOI:10.1007/s40820-019-0310-0

*Corresponding author. E-mail: 1019940752@cpu.edu.cn (Lifang Yin); weihe@cpu.edu.cn (Wei He)

 

Abstract

 


Toc

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 3-fold increase in intracellular level compared to conventional gene carriers, and inhibits the autophagy significantly, along with above 2-fold reduction of LC3II mRNA and approximately 5-fold increase of 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 3-fold increase in apoptosis over that of chemotherapy alone. The anti-tumor study in vivo indicates the combined therapy enables a reduction of 80% in tumor volume and > 2-fold increase of 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 facilitate the delivery of combined therapy of small-molecular drugs and nucleic acids. 


 

Keywords

Nanocrystals; MicroRNA delivery; Autophagy inhibition; Cytotoxicity; Combinatorial therapy

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