摘要
Hypoxia is a hallmark of solid tumors,and it significantly impairs the overall anticancer efficacy,particularly photodynamic therapy(PDT).Herein,a catalase-like nanovesicle with near-infrared light-responsiveness,that is,platinum/gold nanoshell encapsulated chlorin e6(Ce6)/resveratrol(Res)liposome(Pt@Au-Ce6/Res-Lip),was developed to surmount this intractable issue.The Pt@Au-Ce6/Res-Lip can decompose overexpressed H_(2)O_(2)in tumor microenvironment to produce vast amounts of O_(2)for further enhancement of the PDT.Under the 808 nm laser irradiation,the Au nanoshells induced hyperthermia at the lesion site to ablate tumor cells,simultaneously inducing the controlled release of photosensitizer Ce6 and chemotherapeutic agent Res.Moreover,stimulated by 660 nm laser,numerous reactive oxygen species were formed to induce apoptosis and necrosis of tumor cells.With the cascade of trimodal therapeutic modality options(chemotherapy,photothermal therapy,and PDT),the Pt@Au-Ce6/Res-Lip showed ultrahigh tumor inhabitation rate in in vitro and in vivo studies,signifying that the Pt@AuCe6/Res-Lip nanovesicle is a promising candidate for effective cancer therapy.
缺氧作为实体瘤的标志,严重地影响了整体抗肿瘤治疗效果,尤其是光动力疗法.在本文中,我们开发了具有近红外光响应性的类过氧化氢酶纳米囊泡:铂/金纳米壳包覆的二氢卟酚e6(Ce6)/白藜芦醇(Res)脂质体(Pt@Au-Ce6/Res-Lips),以解决这一棘手的问题.Pt@Au-Ce6/Res-Lips可以分解肿瘤微环境中过表达的过氧化氢,从而产生大量氧气,以增强光动力疗法的效果.在808 nm激光照射下,金纳米壳在病变部位产生高热,以消融肿瘤细胞,同时可控地诱导光敏剂Ce6和化疗药物Res的释放.此外,在660 nm激光的刺激下,形成了大量的活性氧(ROS)以诱导肿瘤细胞的凋亡和坏死.随着三重态治疗模式(化疗、光热治疗和光动力治疗)的级联,Pt@Au-Ce6/Res-Lips在体外和体内研究中均显示出超高的肿瘤抑制率,这标志着Pt@Au-Ce6/Res-Lips纳米囊泡将有望成为高效的肿瘤治疗药物.
作者
Liyao Luo
Lei Li
Cong Cong
Yaqian He
Zining Hao
Dawei Gao
骆丽垚;李磊;丛聪;赫雅倩;郝紫泞;高大威(State Key Laboratory of Metastable Materials Science and Technology,Applying Chemistry Key Lab of Hebei Province,Heavy metal deepremediation in water and resource reuse Key Lab of Hebei,Yanshan University,Qinhuangdao 066004,China)
基金
the National Natural Science Foundation(21776238,21476190,and 31801198)
Hebei province Natural fund key projects(B2019203479)。
