2. Academic Validation
  3. Biodegradable oxygen-producing manganese-chelated metal organic frameworks for tumor-targeted synergistic chemo/photothermal/ photodynamic therapy

Biodegradable oxygen-producing manganese-chelated metal organic frameworks for tumor-targeted synergistic chemo/photothermal/ photodynamic therapy

  • Acta Biomater. 2022 Jan 15;138:463-477. doi: 10.1016/j.actbio.2021.10.032.
Lei Feng 1,  Mengyao Chen 1,  Ruihao Li 1,  Lulu Zhou 1,  Chunhui Wang 1,  Pingting Ye 1,  Xiaochun Hu 1,  Jingxian Yang 1,  Yanting Sun 1,  Zhounan Zhu 1,  Kang Fang 1,  Keke Chai 1,  Shuo Shi 2,  Chunyan Dong 3
Affiliations

Affiliations

  • 1 Breast Cancer Center, Shanghai East Hospital, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, China.
  • 2 Breast Cancer Center, Shanghai East Hospital, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, China. Electronic address: shishuo@tongji.edu.cn.
  • 3 Breast Cancer Center, Shanghai East Hospital, School of Medicine, Shanghai Key Laboratory of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, Shanghai 200120, China. Electronic address: cy_dong@tongji.edu.cn.
PMID: 34718179 DOI: 10.1016/j.actbio.2021.10.032
Abstract

Photodynamic therapy (PDT) is an effective noninvasive therapeutic strategy that can convert oxygen to highly cytotoxic singlet oxygen (1O2) through the co-localization of excitation LIGHT and photosensitizers. However, compromised by the hypoxic tumor microenvironment, the therapeutic efficacy of PDT is reduced seriously. Herein, to overcome tumor-associated hypoxia, and further achieve tumor-targeted synergistic chemotherapy/PDT/photothermal therapy (PTT), we have constructed a biodegradable oxygen-producing nanoplatform (named Ini@PM-HP), which was composed of the porous metal-organic framework (PCN-224(Mn)), the poly (ADP-ribose) polymerase (PARP) inhibitor (Iniparib), and the polydopamine-modified hyaluronic acid (HA-PDA). Since HA can specifically bind to the overexpressed HA receptors (cluster determinant 44, CD44) on tumor cell, Ini@PM-HP prefers to accumulate at the tumor site once injected intravenously. Then iniparib can be released in tumor environment (TME), thereby dysfunctioning DNA damage repair and promoting cell Apoptosis. At the same time, the chelating of Mn and tetrakis(4-carboxyphenyl) porphyrin (Mn-TCPP) can generate O2 in situ by reacting with endogenous H2O2, relieving the hypoxic TME and achieving enhanced PDT. Moreover, owing to the high photothermal conversion efficiency of PDA, PTT can be driven by the 808 nm laser irradiation. As systematically demonstrated in vitro and in vivo, this nanotherapeutic approach enables the combined therapy with great inhibition on tumor. Overall, the as-prepared nanoplatform provide a promising strategy to overcome tumor-associated hypoxia, and shows great potential for combination tumor therapy. STATEMENT OF SIGNIFICANCE: A delicately designed biodegradable oxygen-producing nanoplatform Ini@PM-HP is constructed to achieve combination therapy of solid tumors. Taking advantage of the active-targeting, PTT, enhanced PDT and PARPi, this nanotherapeutic approach successfully enables the combined chemo/photothermal/photodynamic therapy with great inhibition of solid tumors.

Keywords

Hypoxia-relieving; Metal organic frameworks; PARP inhibitor; Synergistic therapy.

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