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Drug Nanorod-Mediated Intracellular Delivery of microRNA-101 for Self-sensitization via Autophagy Inhibition
- Source :
- Nano-Micro Letters, Vol 11, Iss 1, Pp 1-16 (2019), Nano-Micro Letters
- Publication Year :
- 2019
- Publisher :
- SpringerOpen, 2019.
-
Abstract
- Highlights Nanosized cytotoxic drug could combat against the autophagy induced by the drug. 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. Electronic supplementary material The online version of this article (10.1007/s40820-019-0310-0) contains supplementary material, which is available to authorized users.<br />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. Electronic supplementary material The online version of this article (10.1007/s40820-019-0310-0) contains supplementary material, which is available to authorized users.
- Subjects :
- Drug
Autophagy inhibition
Materials science
Combinatorial therapy
media_common.quotation_subject
Cytotoxicity
02 engineering and technology
Drug resistance
MicroRNA delivery
lcsh:Technology
Article
03 medical and health sciences
In vivo
microRNA
Electrical and Electronic Engineering
030304 developmental biology
media_common
0303 health sciences
lcsh:T
Autophagy
021001 nanoscience & nanotechnology
Surfaces, Coatings and Films
Electronic, Optical and Magnetic Materials
Nanocrystals
Apoptosis
Cancer cell
Cancer research
Nucleic acid
0210 nano-technology
Subjects
Details
- Language :
- English
- ISSN :
- 21505551 and 23116706
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nano-Micro Letters
- Accession number :
- edsair.doi.dedup.....56e4872601ce581294d5a7368e797ef6