A Hypoxia-Responsive Albumin-Based Nanosystem for Deep Tumor Penetration and Excellent Therapeutic Efficacy

被引：293

作者：

Yang, Guangbao ^{[1
]}

Phua, Soo Zeng Fiona ^{[1
]}

Lim, Wei Qi ^{[1
]}

Zhang, Rui ^{[2
]}

Feng, Liangzhu ^{[2
]}

Liu, Guofeng ^{[1
]}

Wu, Hongwei ^{[1
]}

Bindra, Anivind Kaur ^{[1
]}

Jana, Deblin ^{[1
]}

Liu, Zhuang ^{[2
]}

Zhao, Yanli ^{[1
]}

机构：

[1] Nanyang Technol Univ, Sch Phys & Math Sci, Div Chem & Biol Chem, 21 Nanyang Link, Singapore 637371, Singapore

[2] Soochow Univ, Inst Funct Nano & Soft Mat FUNSOM, Jiangsu Key Lab Carbon Based Funct Mat & Devices, 199 Renai Rd, Suzhou 215123, Jiangsu, Peoples R China

来源：

ADVANCED MATERIALS | 2019年 / 31卷 / 25期

基金：

新加坡国家研究基金会;

关键词：

chemotherapy; human serum albumin; hypoxia; intratumoral penetration; photodynamic therapy; HUMAN SERUM-ALBUMIN; DRUG-DELIVERY; PHOTODYNAMIC THERAPY; FLUORESCENT-PROBES; NANOPARTICLES; MICROENVIRONMENT; AGGREGATION; SYSTEM; GROWTH; CELLS;

D O I：

10.1002/adma.201901513

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Uncontrolled cancer cell proliferation, insufficient blood flow, and inadequate endogenous oxygen lead to hypoxia in tumor tissues. Herein, a unique type of hypoxia-responsive human serum albumin (HSA)-based nanosystem (HCHOA) is reported, prepared by cross-linking the hypoxia-sensitive azobenzene group between photosensitizer chlorin e6 (Ce6)-conjugated HSA (HC) and oxaliplatin prodrug-conjugated HSA (HO). The HCHOA nanosystem is stable under normal oxygen partial pressure with a size of 100-150 nm. When exposed to the hypoxic tumor microenvironment, the nanosystem can quickly dissociate into ultrasmall HC and HO therapeutic nanoparticles with a diameter smaller than 10 nm, significantly enabling their enhanced intratumoral penetration. After the dissociation, the quenched fluorescence of Ce6 in the produced HC nanoparticles can be recovered for bioimaging. At the same time, the production of singlet oxygen is increased because of the enhancement in the photoactivity of the photosensitizer. On account of these improvements, combined photodynamic therapy and chemotherapy is realized to display superior antitumor efficacy in vivo. Based on this simple strategy, it is possible to achieve the dissociation of hypoxic-responsive nanosystem to enhance the tumor penetration and therapeutic effect.

引用

页数：9

共 42 条

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