期刊
ACS APPLIED MATERIALS & INTERFACES
卷 11, 期 43, 页码 39410-39423出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.9b11080
关键词
liposomes; theranostic; photodynamic therapy; hypoxia-activated prodrug; cascade activated
资金
- National Natural Science Foundation of China [21575069, 21602112, 21604042, 21674048, 21904070]
- Ministry of Education of China [IRT1148]
- 333 project of Jiangsu province [BRA2016379]
- Natural Science Foundation of Jiangsu Higher Education Institutions [19KJB150035]
- program for Jiangsu Collaborative Innovation Center of Organic Electronics and Information Displays - Priority Academic Program Development of the Jiangsu Higher Education Institutions [BE2016770]
Photodynamic therapy (PDT) is becoming a promising therapeutic regimen but is limited by the hypoxic microenvironment in solid tumors and the undesirable post-treatment phototoxicity side effects on normal tissues. To overcome these restrictions and enhance the antitumor therapeutic effect, near-infrared (NIR) light-activated, cancer cell-specific, hypoxia prodrug-loaded chlorin e6 liposomes were developed for tumor selective combination therapy guided by multimodal imaging. The photothermal agent indocyanine green (ICG) and hypoxia-activated prodrug tirapazamine (TPZ) were coencapsulated into the liposomes, followed by modification with cRGD and conjugation with Gd-III to form ICG/TPZ@Ce6-GD(III) theranostic liposomes (ITC-GD(III) TLs). In the ITC-GD(III) TLs, both the fluorescence and photodynamic effect of Ce6 were quenched by ICG via fluorescence resonance energy transfer. The ITC-GD(III) TLs can effectively reach the tumor site through the enhanced permeability and retention effect as well as the cRGD-mediated active targeting ability. The fluorescence and photodynamic effect of Ce6 can be activated by the photothermal effect of ICG under NIR light. Upon subsequent irradiation with a 660 nm laser, the released Ce6 could kill cancer cells by generating cytotoxic singlet oxygen. Furthermore, the PDT process would induce hypoxia, which in turn activated the antitumor activity of the codelivered hypoxia-activated prodrug TPZ for a combination antitumor effect. The TLs could be utilized for multimodal imaging (fluorescence/photoacoustic/magnetic resonance imaging)-guided cascade-activated tumor inhibition with optimized therapeutic efficiency and minimized side effects, holding great potential for constructing intelligent nanotheranostics.
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