Engineered biomimetic nanoreactor for synergistic photodynamic-chemotherapy against hypoxic tumor

提拉帕扎明 纳米反应器 光动力疗法 肿瘤缺氧 肿瘤微环境 药物输送 吲哚青绿 化学 活性氧 癌症研究 缺氧(环境) 药理学 细胞毒性 肿瘤细胞 放射治疗 生物化学 医学 体外 病理 氧气 外科 有机化学 催化作用
作者
Haoyu Guo,Lutong Wang,Wei Wu,Mingke Guo,Lingkai Yang,Zhenhao Zhang,Li Cao,Feifei Pu,Xin Huang,Feifei Pu
出处
期刊:Journal of Controlled Release [Elsevier]
卷期号:351: 151-163 被引量:14
标识
DOI:10.1016/j.jconrel.2022.09.020
摘要

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 [email protected] 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.
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