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  3. A multifunctional cascade enzyme system for enhanced starvation/chemodynamic combination therapy against hypoxic tumors

A multifunctional cascade enzyme system for enhanced starvation/chemodynamic combination therapy against hypoxic tumors

  • J Colloid Interface Sci. 2024 Jul 15:666:244-258. doi: 10.1016/j.jcis.2024.04.036.
Zihan Xing 1,  Linwei Li 1,  Tao Liao 1,  Jinyu Wang 1,  Yuhao Guo 1,  Ziqiang Xu 1,  Wenqian Yu 2,  Ying Kuang 3,  Cao Li 4
Affiliations

Affiliations

  • 1 Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei Key Laboratory of Polymer Materials, College of Health Science and Engineering, School of Materials Science and Engineering, Hubei University, Wuhan 430062, China.
  • 2 Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei Key Laboratory of Polymer Materials, College of Health Science and Engineering, School of Materials Science and Engineering, Hubei University, Wuhan 430062, China. Electronic address: wenqianyu@hubu.edu.cn.
  • 3 Hubei Key Laboratory of Industry Microbiology, National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Glyn O. Phillips Hydrocolloid Research Centre at HBUT, School of Life and Health Sciences, Hubei University of Technology, Wuhan 430068, China. Electronic address: lazywawa@163.com.
  • 4 Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei Key Laboratory of Polymer Materials, College of Health Science and Engineering, School of Materials Science and Engineering, Hubei University, Wuhan 430062, China; Hubei Key Laboratory of Industry Microbiology, National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Glyn O. Phillips Hydrocolloid Research Centre at HBUT, School of Life and Health Sciences, Hubei University of Technology, Wuhan 430068, China. Electronic address: licao0415@163.com.
PMID: 38598997 DOI: 10.1016/j.jcis.2024.04.036
Abstract

Starvation therapy has shown promise as a Cancer treatment, but its efficacy is often limited when used alone. In this work, a multifunctional nanoscale cascade Enzyme system, named CaCO3@MnO2-NH2@GOx@PVP (CMGP), was fabricated for enhanced starvation/chemodynamic combination Cancer therapy. CMGP is composed of CaCO3 nanoparticles wrapped in a MnO2 shell, with glucose oxidase (GOx) adsorbed and modified with polyvinylpyrrolidone (PVP). MnO2 decomposes H2O2 in Cancer cells into O2, which enhances the efficiency of GOx-mediated starvation therapy. CaCO3 can be decomposed in the acidic Cancer cell environment, causing CA2+ overload in Cancer cells and inhibiting Mitochondrial Metabolism. This synergizes with GOx to achieve more efficient starvation therapy. Additionally, the H2O2 and gluconic acid produced during glucose consumption by GOx are utilized by MnO2 with catalase-like activity to enhance O2 production and Mn2+ release. This process accelerates glucose consumption, Reactive Oxygen Species (ROS) generation, and CaCO3 decomposition, promoting the CA2+ release. CMGP can alleviate tumor hypoxia by cycling the enzymatic cascade reaction, which increases Enzyme activity and combines with CA2+ overload to achieve enhanced combined starvation/chemodynamic therapy. In vitro and in vivo studies demonstrate that CMGP has effective Anticancer abilities and good biosafety. It represents a new strategy with great potential for combined Cancer therapy.

Keywords

Ca(2+) overload; Chemodynamic therapy; Combined cancer therapy; Nanoenzymatic cascade system; Starvation therapy.

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