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ACS Nano. 2019 Jun 25;13(6):7333-7344. doi: 10.1021/acsnano.9b03846. Epub 2019 Jun 12.

Triplex DNA Nanoswitch for pH-Sensitive Release of Multiple Cancer Drugs.

Chen X1,2, Chen T1, Ren L1, Chen G1,3, Gao X3, Li G1,4, Zhu X1.

Author information

1
Center for Molecular Recognition and Biosensing, School of Life Sciences , Shanghai University , Shanghai 200444 , P. R. China.
2
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine , Shanghai Jiao Tong University , Shanghai 200032 , P. R. China.
3
Department of Bioengineering , University of Washington , Seattle , Washington 98195 , United States.
4
State Key Laboratory of Pharmaceutical Biotechnology and Collaborative Innovation Center of Chemistry for Life Sciences, Department of Biochemistry , Nanjing University , Nanjing 210093 , P. R. China.

Abstract

A DNA-based stimulus-responsive drug delivery system for synergetic cancer therapy has been developed. The system is built on a triplex-DNA nanoswitch capable of precisely responding to pH variations in the range of ∼5.0-7.0. In extracellular neutral pH space, the DNA nanoswitch keeps a linear conformation, immobilizing multiple therapeutics such as small molecules and antisense compounds simultaneously. Following targeted cancer cell uptake via endocytosis, the nanoswitch inside acidic intracellular compartments goes through a conformational change from linear to triplex, leading to smart release of the therapeutic combination. This stimuli-responsive drug delivery system does not rely on artificial responsive materials, making it biocompatible. Furthermore, it enables simultaneous delivery of multiple therapeutics for enhanced efficacy. Using tumor-bearing mouse models, we show efficient gene silencing and significant inhibition of tumor growth upon intravenous administration of the smart nanoswitch, providing opportunities for combinatorial cancer therapy.

KEYWORDS:

DNA; cancer therapy; drug delivery; nanomaterials; stimuli-response

PMID:
31180197
DOI:
10.1021/acsnano.9b03846

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