TY - JOUR
T1 - Programming Drug Delivery Kinetics for Active Burst Release with DNA Toehold Switches
AU - Xiao, Mingshu
AU - Lai, Wei
AU - Wang, Fei
AU - Li, Li
AU - Fan, Chunhai
AU - Pei, Hao
N1 - Publisher Copyright:
Copyright © 2019 American Chemical Society.
PY - 2019/12/26
Y1 - 2019/12/26
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85076791169
U2 - 10.1021/jacs.9b10765
DO - 10.1021/jacs.9b10765
M3 - 文章
C2 - 31790242
AN - SCOPUS:85076791169
SN - 0002-7863
VL - 141
SP - 20354
EP - 20364
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 51
ER -
