Biomimetic ZIF8 Nanosystem With Tumor Hypoxia Relief Ability to Enhance Chemo-Photothermal Synergistic Therapy

Ziming Zhao; Zhaorong Liu; Yabing Hua; Yuanjie Pan; Ge Yi; Shengyue Wu; Cong He; Yanzhuo Zhang; Yihua Yang

doi:10.3389/fphar.2022.850534

Biomimetic ZIF8 Nanosystem With Tumor Hypoxia Relief Ability to Enhance Chemo-Photothermal Synergistic Therapy

Front Pharmacol. 2022 Mar 24:13:850534. doi: 10.3389/fphar.2022.850534. eCollection 2022.

Authors

Ziming Zhao^{1

2}, Zhaorong Liu¹, Yabing Hua^{1

2}, Yuanjie Pan¹, Ge Yi¹, Shengyue Wu¹, Cong He¹, Yanzhuo Zhang^{1

2}, Yihua Yang^{1

2}

Affiliations

¹ Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.
² Department of Pharmaceutics, School of Pharmacy, Xuzhou Medical University, Xuzhou, China.

Abstract

Tumor hypoxic microenvironment can reduce the therapeutic effects of chemotherapy, radiotherapy, photodynamic therapy, immunotherapy, etc. It is also a potential source of tumor recurrence and metastasis. A biomimetic nanosystem based on zeolitic imidazolate framework 8 (ZIF8), which had multifunctions of hypoxia relief, chemotherapy, and photothermal therapy, was established to improve tumor hypoxic microenvironment and overcome the corresponding therapeutic resistance. ZIF8 enveloped with DOX and CuS nanoparticles (DC@ZIF8) was synthesized by a sedimentation method. Red blood cell membrane and catalase (CAT) were coated onto DC@ZIF8 and biomimetic nanosystem (DC@ZIF8-MEM_C) was formed. The designed DC@ZIF8-MEM_C had a shape of polyhedron with an average particle size around 254 nm. The loading content of DOX, CAT, and CuS was 4.9%, 6.2%, and 2.5%, separately. The release of DOX from DC@ZIF8-MEM_C was pH dependent and significantly faster at pH 5 due to the degradation of ZIF8. DC@ZIF8-MEM_C exhibited outstanding photothermal conversion properties and excellent antitumor effect in vitro and in vivo. Moreover, the hypoxia relief by CAT was proved to have good sensitization effect on chemo-photothermal combined therapy. DC@ZIF8-MEM_C is a prospective nanosystem, which can realize great chemo-photothermal synergistic antitumor effect under the sensitization of CAT. The biomimetic multifunctional nanoplatform provides a potential strategy of chemo-photothermal synergistic antitumor effect under the sensitization of CAT.

Keywords: ZIF8; biomimetic; chemotherapy; hypoxia relief; photothermal therapy.