Cancer-Selective Bioreductive Chemotherapy Mediated by Dual Hypoxia-Responsive Nanomedicine upon Photodynamic Therapy-Induced Hypoxia Aggravation

Rongying Zhu, Hua He, Yong Liu, Desheng Cao, Jin Yan, Shanzhou Duan, Yongbing Chen, Lichen Yin

    Research output: Contribution to journalArticleAcademicpeer-review

    20 Citations (Scopus)

    Abstract

    Stimuli-responsive drug delivery has rendered promising utilities in cancer treatment. Nevertheless, cancer selectivity as well as sensitivity still remains critical challenges that would undermine the therapeutic efficacy of chemodrugs and cause undesired systemic toxicity. Herein, a dual hypoxia-responsive drug delivery system was developed to enable photodynamic therapy (PDT)-induced drug release and drug activation intermediated via PDT-induced hypoxia. Particularly, tumor-targeting and hypoxia-dissociable nanoparticles (NPs) were self-assembled from the amphiphilic polyethylenimine-alkyl nitroimidazole [PEI-ANL (PA)] and hyaluronic acid-chlorin e6 (HA-Ce6) to encapsulate bioreductive chemodrug, tirapazamine (TPZ). After systemic administration, the obtained PA/HA-Ce6@TPZ NPs enabled effective tumor accumulation due to HA-mediated cancer targeting. Upon receptor-mediated endocytosis, light irradiation (660 nm, 10 mW/cm(2)) produced high levels of reactive oxygen species to mediate PDT and generated a severe local hypoxic environment to dissociate the NPs and selectively release TPZ, as a consequence of hypoxia-triggered hydrophobic-to-hydrophilic transformation of ANI. In the meantime, TPZ was activated under hypoxia, finally contributing to a synergistic anticancer treatment between PDT and hypoxia-strengthened bioreductive chemotherapy. This study, therefore, demonstrates a suitable strategy for cancer-selective drug delivery as well as programmed combination therapy.

    Original languageEnglish
    Pages (from-to)2649-2656
    Number of pages8
    JournalBiomacromolecules
    Volume20
    Issue number7
    DOIs
    Publication statusPublished - Jul-2019

    Keywords

    • THERANOSTIC LIPOSOMES
    • DRUG-DELIVERY
    • NANOPARTICLES
    • PRODRUG
    • DOXORUBICIN
    • VESICLES

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