Dual-Targeted Nanoreactors and Prodrugs: Hydrogen Peroxide Triggers Oxidative Damage and Prodrug Activation for Synergistic Elimination of Cancer Cells

Seong Min Jo, Hyeong Seok Kim, Miae Won, Carole Champanhac, Jong Seung Kim, Frederik R. Wurm*, Katharina Landfester

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

22 Citations (Scopus)
130 Downloads (Pure)

Abstract

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.

Original languageEnglish
Article number2200791
JournalAdvanced functional materials
Volume32
Issue number26
Early online date23 Mar 2022
DOIs
Publication statusPublished - 24 Jun 2022

Keywords

  • chemodynamic therapeutics, dual-targeting
  • nanoreactors, ROS-responsive prodrugs, synergistic cancer therapy
  • UT-Hybrid-D

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