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靶向分级纳米颗粒改善肿瘤乏氧微环境并增强光动力学癌症治疗

Grade-targeted nanoparticles for improved hypoxic tumor microenvironment and enhanced photodynamic cancer therapy.

机构信息

Department of Clinical Medicine, Xuzhou Medical University, Xuzhou 221004, China.

Department of Dermatology, Changzhou First People's Hospital, Changzhou 213000, China.

出版信息

Nanomedicine (Lond). 2021 Feb;16(3):221-235. doi: 10.2217/nnm-2020-0096. Epub 2021 Feb 3.

Abstract

The hypoxia of the tumor microenvironment (TME), low transfer efficiency of photosensitizers and limited diffusion distance of reactive oxygen species restrict the application of photodynamic therapy (PDT). To produce TME-responsive and effective nanoparticles for sensitizing PDT. CD44 and mitochondria grade-targeted hyaluronic acid (HA)-triphenylphosphine (TPP)-aminolevulinic acid (ALA)-catalase (CAT) nanoparticles (HTACNPs) were synthesized via a modified double-emulsion method. and experiments were performed to investigate the antitumor efficacy of HTACNP-mediated PDT. HTACNPs specifically targeted MV3 cells and the mitochondria and produced O to relieve TME hypoxia. HTACNP-mediated PDT produced reactive oxygen species to induce irreversible cell apoptosis. HTACNP-PDT inhibited melanoma growth effectively . HTACNP-mediated PDT improved TME hypoxia and effectively enhanced PDT for cancer.

摘要

肿瘤微环境(TME)的缺氧、光敏剂的低转移效率和活性氧的扩散距离有限,限制了光动力疗法(PDT)的应用。为了制备 TME 响应的有效纳米颗粒用于光敏化 PDT,通过改良的双重乳液法合成了 CD44 和线粒体分级靶向透明质酸(HA)-三苯基膦(TPP)-氨基酮戊酸(ALA)-过氧化氢酶(CAT)纳米颗粒(HTACNPs),并进行了实验研究 HTACNP 介导的 PDT 的抗肿瘤功效。HTACNPs 特异性靶向 MV3 细胞和线粒体,并产生 O 以缓解 TME 缺氧。HTACNP 介导的 PDT 产生活性氧诱导不可逆的细胞凋亡。HTACNP-PDT 有效抑制黑色素瘤生长。HTACNP 介导的 PDT 改善 TME 缺氧,有效增强癌症 PDT。

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