Programming Drug Delivery Kinetics for Active Burst Release with DNA Toehold Switches
2019
Xiao, Mingshu | Lai, Wei | Wang, Fei | Li, Li | Fan, Chunhai | Pei, Hao
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 t₁/₂ 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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