期刊
BIOMATERIALS
卷 141, 期 -, 页码 40-49出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2017.06.031
关键词
NIR; Caspase-3; Photodynamic therapy; Cascade chemotherapy; Upconversion nanoparticles
资金
- Key Program of the National Natural Scientific Foundation of China (NSFC) [81630046]
- NSFC Project of International Cooperation and Exchanges [61361160414]
- NSFC Project [21674040, 51403042, 81371646]
- Natural Science Foundation for Distinguished Young Scholars of Guangdong Province [2016A030306013]
- Guangdong Program for Support of Top-notch Young Professionals [2015TQ01R604]
- Natural Science Foundation of Guangdong Province [2014A030310310]
- Scientific Research Projects of Guangzhou [201607010328]
Stimuli-responsive nanoparticles with multiple therapeutic/diagnostic functions are highly desirable for effective tumor treatment. Herein novel caspase-3 responsive functionalized upconversion nanoparticles (CFUNs) were fabricated with three-in-one functional integration: near-infrared (NIR) triggered photo dynamic damage along with caspase-3 activation, subsequent caspase-3 responsive drug release, and cascade chemotherapeutic activation. CFUNs were formulated from the self-assembly of caspase-3 responsive doxorubicin (DOX) prodrug tethered with DEVD peptide (DEVD-DOX), upconversion nano particles (UCNP), a photosensitizer (pyropheophorbide-a methyl ester, MPPa), and tumor-targeting cRGD-PEG-DSPE to afford multifunctional CFUNs, MPPa/UCNP-DEVD-DOX/cRGD. Upon cellular uptake and NIR irradiation, the visible light emission of UCNP could excite MPPa to produce reactive oxygen species for photodynamic therapy (PDT) along with the activation of caspase-3, which further cleaved DEVD peptide to release DOX within tumor cells, thus accomplishing NIR-triggered PDT and cascade chemotherapy. CFUNs presented silent therapeutic potency and negligible cytotoxicity in the dark, whereas in vitro and in vivo experiments demonstrated the NIR-triggered cascade therapeutic activation and tumor inhibition due to consecutive PDT and chemotherapy. Current NIR-activated cascade tumor therapy with two distinct mechanisms is significantly favorable to overcome multidrug resistance and tumor heterogeneity for persistent tumor treatment. (C) 2017 Elsevier Ltd. All rights reserved.
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