Triplex DNA Nanoswitch for pH-Sensitive Release of Multiple Cancer Drugs.
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.
['Chen|Xiaoxia|X|', 'Chen|Tianshu|T|', 'Ren|Lingjie|L|', 'Chen|Guifang|G|', 'Gao|Xiaohu|X|0000-0002-6054-0530', 'Li|Genxi|G|0000-0001-9663-9914', 'Zhu|Xiaoli|X|0000-0001-5497-4538']
D000818:Animals D000970:Antineoplastic Agents D052157:Aptamers, Nucleotide D004247:DNA D065546:Drug Liberation D006367:HeLa Cells D006801:Humans D006863:Hydrogen-Ion Concentration D061986:MCF-7 Cells D051379:Mice D053758:Nanoparticles D009374:Neoplasms, Experimental D000080762:Stimuli Responsive Polymers
DNA drug delivery cancer therapy stimuli-response nanomaterials