Journal
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume 141, Issue 51, Pages 20354-20364Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jacs.9b10765
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Funding
- National Science Foundation of China [21722502]
- National Key Research and Development Program of China for International Science & Innovation Cooperation Major Project between Governments [2018YFE0113200]
- Shanghai Rising-Star Program [19QA1403000]
- Shanghai Science and Technology Committee (STCSM) [18490740500]
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Despite smart drug delivery systems (DDSs) with high delivery efficiency and improved efficacy for chemotherapy, precise drug release in targeted tumor cells in a controllable way is still challenging. In this work, we develop DNA toehold switch-engineered spherical nucleic acid-templated hydrogel (SNAgel) for on-site active burst release of chemotherapeutic (tumor-killing) drugs in target cancer cells. By designing ligand-specific toehold sequences on hybridization chain reaction (HCR)-generated SNAgel, we realize burst release of payloads with a wide range of t(1/2) ranging from 60.52 to 5.49 min by active dynamic control of the kinetics. The camouflage of SNAgels with compact DNA shell enables elongated/prolonged blood circulation and targeted accumulation, cell entry, and apoptosis induction in vivo. The enhanced anticancer activity of SNAgels was substantiated in both cancer cell lines and xenografted tumor-bearing mice. This DNA-engineered kinetic control approach sheds new light on developing paradigm-shifting DDSs for cancer therapeutics.
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