An Oxygen Self-sufficient Fluorinated Nanoplatform for Relieved Tumor Hypoxia and Enhanced Photodynamic Therapy of Cancers

被引:73
|
作者
Ma, Shengnan [2 ]
Zhou, Jie [2 ]
Zhang, Yuxin [2 ]
Yang, Bo [1 ]
He, Yiyan [1 ,2 ]
Tian, Chen [1 ]
Xu, Xianghui [1 ,2 ]
Gu, Zhongwei [1 ,2 ]
机构
[1] Nanjing Tech Univ, Coll Mat Sci & Engn, 30 Puzhu Rd S, Nanjing 211816, Jiangsu, Peoples R China
[2] Sichuan Univ, Natl Engn Res Ctr Biomat, 29 Wangjiang Rd, Chengdu 610064, Sichuan, Peoples R China
基金
中国国家自然科学基金; 中国博士后科学基金;
关键词
oxygen self-sufficient; tumor oxygenation; tumor penetration; photodynamic therapy; orthotopic breast cancer; HIGHLY EFFICIENT; IN-VIVO; NANOPARTICLES; PENETRATION; NANOCOMPOSITES; NANOMEDICINE; ACCUMULATION; RESISTANCE; EFFICACY; LIGHT;
D O I
10.1021/acsami.8b19840
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
The efficacy of photodynamic therapy (PDT) in the solid tumor is hampered by many challenges, including its oxygen self-consuming nature, insufficient oxygen levels within the hypoxic tumor microenvironment, and limited penetration of photosensitizers within tumors. Herein, we develop the IR780@O-2-SFNs/iRGD as an oxygen self-sufficient and tumor-penetrating nanoplatform, which consists of IR780-loaded pH-sensitive fluorocarbon-functionalized nanoparticles (SFNs) and iRGD as a tumor targeting peptide that can penetrate deeper within the tumor. Because of the high oxygen affinity and outstanding permeability of the obtained nanoplatform, oxygen and IR780 which are encapsulated in the same core can play their roles to the utmost, resulting in remarkably accelerated singlet oxygen production, as demonstrated in vitro by the 3D multicellular spheroids and in vivo by tumor tissues. More interestingly, a single-dose intravenous administration of IR780@O-2-SFNs/iRGD into mice bearing orthotopic breast cancer could selectively accumulate at the tumor site, highly alleviate the tumor hypoxia, significantly inhibit the primary tumor growth, and reduce the lung and liver metastasis, enabling the improved photodynamic therapeutic performance. Thus, this work paves an effective way to improve PDT efficacy through increasing tumor oxygenation and selective delivery of photosensitizers to the deep and hypoxic tumor.
引用
收藏
页码:7731 / 7742
页数:12
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