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Biomimetic Liposomal Nanoplatinum for Targeted Cancer Chemophototherapy
Advanced Science ( IF 15.1 ) Pub Date : 2021-03-01 , DOI: 10.1002/advs.202003679
Xue-Liang Liu 1 , Xiao Dong 1 , Si-Cong Yang 1 , Xing Lai 1 , Hai-Jun Liu 1 , Yuhao Gao 1 , Hai-Yi Feng 1 , Mao-Hua Zhu 1 , Yihang Yuan 1 , Qin Lu 1 , Jonathan F Lovell 2 , Hong-Zhuan Chen 3 , Chao Fang 1
Affiliation  

Photodynamic therapy (PDT) of cancer is limited by tumor hypoxia. Platinum nanoparticles (nano‐Pt) as a catalase‐like nanoenzyme can enhance PDT through catalytic oxygen supply. However, the cytotoxic activity of nano‐Pt is not comprehensively considered in the existing methods to exert their multifunctional antitumor effects. Here, nano‐Pt are loaded into liposomes via reverse phase evaporation. The clinical photosensitizer verteporfin (VP) is loaded in the lipid bilayer to confer PDT activity. Murine macrophage cell membranes are hybridized into the liposomal membrane to confer biomimetic and targeting features. The resulting liposomal system, termed “nano‐Pt/VP@MLipo,” is investigated for chemophototherapy in vitro and in vivo in mouse tumor models. At the tumor site, oxygen produced by nano‐Pt catalyzation improves the VP‐mediated PDT, which in turn triggers the release of nano‐Pt via membrane permeabilization. The ultrasmall 3–5 nm nano‐Pt enables better penetration in tumors, which is also facilitated by the generated oxygen gas, for enhanced chemotherapy. Chemophototherapy with a single injection of nano‐Pt/VP@MLipo and light irradiation inhibits the growth of aggressive 4T1 tumors and their lung metastasis, and prolongs animal survival without overt toxicity.

中文翻译:

用于靶向癌症化疗光疗的仿生脂质体纳米铂

癌症的光动力疗法(PDT)受到肿瘤缺氧的限制。铂纳米颗粒(nano-Pt)作为一种类似过氧化氢酶的纳米酶,可以通过催化供氧来增强 PDT。然而,现有方法并未全面考虑纳米Pt的细胞毒活性,以发挥其多功能抗肿瘤作用。在这里,纳米铂通过反相蒸发装载到脂质体中。将临床光敏剂维替泊芬 (VP) 加载到脂质双层中以赋予 PDT 活性。鼠巨噬细胞膜与脂质体膜杂交,以赋予仿生和靶向特征。由此产生的脂质体系统被称为“nano-Pt/VP@MLipo”,在小鼠肿瘤模型中进行体外和体内化学光疗研究。在肿瘤部位,纳米铂催化产生的氧气改善了 VP 介导的 PDT,进而通过膜透化作用触发纳米铂的释放。超小的 3-5 nm 纳米铂能够更好地渗透到肿瘤中,产生的氧气也有利于增强化疗。单次注射纳米 Pt/VP@MLipo 和光照射的化学光疗可抑制侵袭性 4T1 肿瘤的生长及其肺转移,并延长动物的生存期,且无明显毒性。
更新日期:2021-04-22
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