TY - JOUR
T1 - Dual-Targeted Nanoreactors and Prodrugs
T2 - Hydrogen Peroxide Triggers Oxidative Damage and Prodrug Activation for Synergistic Elimination of Cancer Cells
AU - Jo, Seong Min
AU - Kim, Hyeong Seok
AU - Won, Miae
AU - Champanhac, Carole
AU - Kim, Jong Seung
AU - Wurm, Frederik R.
AU - Landfester, Katharina
N1 - Funding Information:
S‐M.J. and H.S.K. contributed equally to this work. This work was part of the MaxSynBio consortium, jointly funded by the Federal Ministry of Education and Research of Germany and the Max Planck Society. This work was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (CRI Project No. 2018R1A3B1052702 and 2019M3E5D1A01068998, J.S.K.), Basic Science Research Program (2020R1A6A3A01100551, M.W.) funded by the Ministry of Education. The authors sincerely thank Dr. Robert Graf (MPIP) for solid‐state NMR spectroscopy studies. The authors thank Ute Heinz (MPIP) and Petra Räder (MPIP) for analytical support.
Publisher Copyright:
© 2022 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH.
PY - 2022/6/24
Y1 - 2022/6/24
N2 - Synergistic strategies by combining nanoreactors and prodrugs hold tremendous potential in anticancer treatment. However, precise death of target cancer cells remains a significant challenge due to the absence of an elaborate cancer targeting strategy. Here, a dual-targeting approach that combines the action of H2O2-producing folate receptor-targeted nanoreactors with a cyclooxygenase-2 (COX-2) targeted prodrug is reported. A folate-modified silica nanoreactor encapsulating glucose oxidase (GOX) is prepared to generate H2O2, which induces oxidative stress and allows the activation of the prodrug by targeted intracellular delivery. A novel prodrug bearing both COX-2 targeting Celecoxib and SN-38 anticancer agent with an H2O2-cleavable thioketal linker to activate the drug is presented. By dual-targeting, the generated H2O2 from GOX triggers the cleavage of a thioketal linker in the prodrug to produce the active form of the SN-38 anticancer drug in cancer cells inducing synergistic cell death. This dual-targeting strategy with a synergistic potency can aid in developing selective and effective anticancer therapeutics.
AB - Synergistic strategies by combining nanoreactors and prodrugs hold tremendous potential in anticancer treatment. However, precise death of target cancer cells remains a significant challenge due to the absence of an elaborate cancer targeting strategy. Here, a dual-targeting approach that combines the action of H2O2-producing folate receptor-targeted nanoreactors with a cyclooxygenase-2 (COX-2) targeted prodrug is reported. A folate-modified silica nanoreactor encapsulating glucose oxidase (GOX) is prepared to generate H2O2, which induces oxidative stress and allows the activation of the prodrug by targeted intracellular delivery. A novel prodrug bearing both COX-2 targeting Celecoxib and SN-38 anticancer agent with an H2O2-cleavable thioketal linker to activate the drug is presented. By dual-targeting, the generated H2O2 from GOX triggers the cleavage of a thioketal linker in the prodrug to produce the active form of the SN-38 anticancer drug in cancer cells inducing synergistic cell death. This dual-targeting strategy with a synergistic potency can aid in developing selective and effective anticancer therapeutics.
KW - chemodynamic therapeutics, dual-targeting
KW - nanoreactors, ROS-responsive prodrugs, synergistic cancer therapy
UR - http://www.scopus.com/inward/record.url?scp=85126864998&partnerID=8YFLogxK
U2 - 10.1002/adfm.202200791
DO - 10.1002/adfm.202200791
M3 - Article
AN - SCOPUS:85126864998
SN - 1616-301X
VL - 32
JO - Advanced Functional Materials
JF - Advanced Functional Materials
IS - 26
M1 - 2200791
ER -
