期刊
THERANOSTICS
卷 6, 期 4, 页码 456-469出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.14101
关键词
ROS-sensitive nanoparticles; photodynamic therapy; Camptothecin; UCNPs; orthotopic lung cancer
资金
- National Key Basic Research Program (973 Project) [2015CB931802]
- National Natural Scientific Foundation of China [81225010, 81327002, 1170961]
- 863 project of China [2014AA020700]
- Shanghai Science and Technology Fund [13NM1401500, 15DZ2252000]
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [F31AA020700] Funding Source: NIH RePORTER
Many drug controlled release methods have been integrated in multifunctional nanoparticles, such as pH-, redox-, temperature-, enzyme-, and light-responsive release. However, few report is associated with the ROS responsive drug controlled release. Herein, a thioketal linker-based ROS responsive drug (camptothecin conjugated with thioketal linker, abbreviated as TL-CPT) was prepared and the thioketal linker could be cleaved by ROS(reactive oxygen species). To achieve cancer simultaneous optical imaging, photodynamic therapy and chemotherapy, the photosensitizer Chlorin e6(Ce6), TL-CPT and carboxyl-mPEG were loaded on the upconversion nanoparticles (UCNPs), which were named as Ce6-CPT-UCNPs. Under 980 nm laser irradiation, Ce6-CPT-UCNPs emitted a narrow emission band at 645-675 nm which was overlapped with Ce6 absorption peak. Ce6 absorbed the light to produce ROS, which was used for photodynamic therapy and to cleave the thioketal linker in Ce6-CPT-UCNPs to release camptothecin for chemotherapy. Meanwhile, Ce6 absorbed the light, was used for near-infrared fluorescence imaging. The in vivo biodistribution studies showed that the prepared nanoparticles had high orthotopic lung cancer targeting efficiency. The in vivo therapeutic results demonstrated that NCI-H460 lung cancers could be completely eliminated by combining chemo-and photodynamic therapy under 980 nm laser irradiation. The prepared multifunctional Ce6-CPT-UCNPs have great potential in applications such as cancer targeted fluorescent imaging, simultaneous ROS activated chemo-and photodynamic therapy in near future.
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