Tumor-microenvironment-responsive poly-prodrug encapsulated semiconducting polymer nanosystem for phototherapy-boosted chemotherapy

Jianwei Zhu, Yuning Zhang, Zheng Li, Xiaowen Bao, Yanfeng Zhou, Bo Ma, Ying Xie, Peiyu Yan, Zimei Wu, Qi Zhang, Jianhua Zou, Xiaoyuan Chen

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Phototherapy-induced hypoxia in the tumor microenvironment (TME) is responsible for diminished therapeutic efficacy. Designing an intelligent nanosystem capable of responding to hypoxia for TME-responsive drug delivery will, to some extent, improve the therapeutic efficacy and reduce side effects. Semiconducting polymers with high photothermal conversion efficiency and photostability have tremendous potential as phototheranostics. In this paper, hypoxia-activatable tirapazamine (TPZ) was conjugated onto poly(ethylene glycol) to form a pH-sensitive poly-prodrug, PEG-TPZ, that can be triggered by the low acidity of the TME to cleave the acylamide bond for controllable drug release. PEG-TPZ was then used to encapsulate a semiconducting polymer (TDPP) for NIR-II-fluorescence-imaging-guided synergistic therapy. The reactive oxygen species (ROS) generation and ultrahigh photothermal conversion efficiency (∼58.6%) of the TDPP@PEG-TPZ NPs leads to the destruction of the tumor blood vessels, thus further activating the hypoxia-induced chemotherapy of TPZ. As a result, effective tumor regression was achieved after laser irradiation.

Original languageEnglish
Pages (from-to)3014-3023
Number of pages10
JournalMaterials Horizons
Volume10
Issue number8
DOIs
StatePublished - 3 May 2023

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