Polydopamine-coated UiO-66 nanoparticles loaded with perfluorotributylamine/tirapazamine for hypoxia-activated osteosarcoma therapy

被引：51

作者：

Chen, Hongfang ^{[1
]}

Fu, You ^{[2
,3
,4
,5
,6
]}

Feng, Kai ^{[7
]}

Zhou, Yifan ^{[1
]}

Wang, Xin ^{[1
]}

Huang, Haohan ^{[1
]}

Chen, Yan ^{[1
]}

Wang, Wenhao ^{[8
]}

Xu, Yuanjing ^{[9
]}

Tian, Haijun ^{[1
]}

Mao, Yuanqing ^{[1
]}

Wang, Jinwu ^{[1
]}

Zhang, Zhiyuan ^{[2
,3
,4
,5
,6
]}

机构：

[1] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Orthopaed Surg, Shanghai Key Lab Orthopaed Implants,Sch Med, Shanghai 200011, Peoples R China

[2] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 9, Dept Oral & Maxillofacial Head & Neck Oncol, Sch Med, Shanghai, Peoples R China

[3] Shanghai Jiao Tong Univ, Coll Stomatol, Shanghai, Peoples R China

[4] Natl Ctr Stomatol, Shanghai, Peoples R China

[5] Natl Clin Res Ctr Oral Dis, Shanghai, Peoples R China

[6] Shanghai Key Lab Stomatol, Shanghai, Peoples R China

[7] Shanghai Jiaotong Univ Affiliated Peoples Hosp 6, Dept Orthoped Surg, Inst Microsurg Extrem, Shanghai, Peoples R China

[8] Southwest Jiaotong Univ, Coll Med, Chengdu, Peoples R China

[9] Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai, Peoples R China

来源：

JOURNAL OF NANOBIOTECHNOLOGY | 2021年 / 19卷 / 01期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

Metal-organic framework (MOF); Tumor hypoxia; Photothermal therapy (PTT); Osteosarcoma; METAL-ORGANIC-FRAMEWORK; PHOTODYNAMIC THERAPY; LIVER METASTASIS; PROGRESSION; DELIVERY; PLATFORM; REMOVAL;

D O I：

10.1186/s12951-021-01013-0

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Background Hypoxia is a characteristic of solid tumors that can lead to tumor angiogenesis and early metastasis, and addressing hypoxia presents tremendous challenges. In this work, a nanomedicine based on oxygen-absorbing perfluorotributylamine (PFA) and the bioreductive prodrug tirapazamine (TPZ) was prepared by using a polydopamine (PDA)-coated UiO-66 metal organic framework (MOF) as the drug carrier. Results The results showed that TPZ/PFA@UiO-66@PDA nanoparticles significantly enhanced hypoxia, induced cell apoptosis in vitro through the oxygen-dependent HIF-1 alpha pathway and decreased oxygen levels in vivo after intratumoral injection. In addition, our study demonstrated that TPZ/PFA@UiO-66@PDA nanoparticles can accumulate in the tumor region after tail vein injection and effectively inhibit tumor growth when combined with photothermal therapy (PTT). TPZ/PFA@UiO-66@PDA nanoparticles increased HIF-1 alpha expression while did not promote the expression of CD31 in vivo during the experiment. Conclusions By using TPZ and PFA and the enhanced permeability and retention effect of nanoparticles, TPZ/PFA@UiO-66@PDA can target tumor tissues, enhance hypoxia in the tumor microenvironment, and activate TPZ. Combined with PTT, the growth of osteosarcoma xenografts can be effectively inhibited.

引用

页数：18

共 51 条

[1] Encapsulation of aggregated gold nanoclusters in a metal-organic framework for real-time monitoring of drug release [J].