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  2. Engineered biomimetic nanoreactor for synergistic photodynamic-chemotherapy against hypoxic tumor

Engineered biomimetic nanoreactor for synergistic photodynamic-chemotherapy against hypoxic tumor

  • J Control Release. 2022 Sep 22;351:151-163. doi: 10.1016/j.jconrel.2022.09.020.
Haoyu Guo 1 Lutong Wang 1 Wei Wu 1 Mingke Guo 2 Lingkai Yang 1 Zhenhao Zhang 1 Li Cao 1 Feifei Pu 1 Xin Huang 3 Zengwu Shao 4
Affiliations

Affiliations

  • 1 Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
  • 2 Department of Orthopaedics, Affiliated Hospital of NCO school of Army Medical University, Shijiazhuang 050041, China.
  • 3 Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: xin_huang@hust.edu.cn.
  • 4 Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: 1985XH0536@hust.edu.cn.
Abstract

Photodynamic therapy (PDT) can produce a large amount of Reactive Oxygen Species (ROS) in the radiation field to kill tumor cells. However, the sustainable anti-tumor efficacy of PDT is limited due to the hypoxic microenvironment of tumor. In this study, classic PDT agent indocyanine green (ICG) and hypoxia-activated chemotherapeutic drug tirapazamine (TPZ) were loaded on mesoporous polydopamine (PDA) to construct PDA@ICG-TPZ nanoparticles (PIT). Then, PIT was camouflaged with cyclic arginine-glycine-aspartate (cRGD) modified tumor cell membranes to obtain the engineered membrane-coated nanoreactor (cRGD-mPIT). The nanoreactor cRGD-mPIT could achieve the dual-targeting ability via tumor cell membrane mediated homologous targeting and cRGD mediated active targeting. With the enhanced tumor-targeting and penetrating delivery system, PIT could efficiently accumulate in hypoxic tumor cells and the loaded drugs were quickly released in response to near-infrared (NIR) laser. The nanoreactor might produce cytotoxic ROS under NIR and further enhance hypoxia within tumor to activate TPZ, which efficiently inhibited hypoxic tumor by synergistic photodynamic-chemotherapy. Mechanically, hypoxia-inhibitory factor-1α (HIF-1α) was down-regulated by the synergistic therapy. Accordingly, the cRGD-mPIT nanoreactor with sustainable and cascade anti-tumor effects and satisfied biosafety might be a promising strategy in hypoxic tumor therapy.

Keywords

Cell membrane-coated nanotechnology; Hypoxic tumor; Synergistic photodynamic-chemotherapy; Targeted delivery system.

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