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

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.

• Authors: Xiaoxia Chen, Tianshu Chen, Lingjie Ren, Guifang Chen, Xiaohu Gao, Genxi Li, Xiaoli Zhu
• Journal: ACS nano (ACS Nano) Vol. 13 Issue 6 Pg. 7333-7344 (06 25 2019) ISSN: 1936-086X [Electronic] United States
• PMID: 31180197 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Aptamers, Nucleotide
• Stimuli Responsive Polymers
• DNA

Topics

• Animals
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Aptamers, Nucleotide (chemistry)
• DNA (chemistry)
• Drug Liberation
• HeLa Cells
• Humans
• Hydrogen-Ion Concentration
• MCF-7 Cells
• Mice
• Nanoparticles (chemistry)
• Neoplasms, Experimental (drug therapy)
• Stimuli Responsive Polymers (chemistry)