Theranostics 2016; 6(4):456-469. doi:10.7150/thno.14101

Research Paper

Near-Infrared Light Triggered ROS-activated Theranostic Platform based on Ce6-CPT-UCNPs for Simultaneous Fluorescence Imaging and Chemo-Photodynamic Combined Therapy

Caixia Yue1,2, Chunlei Zhang1, Gabriel Alfranca1, Yao Yang1, Xinquan Jiang3, Yuming Yang1✉, Fei Pan1, Jesús M. de la Fuente1, Daxiang Cui1,4✉

1. Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science & Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P. R. China;
2. School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P. R. China;
3. Department of Prosthodontics, Oral Bioengineering and Regenerative Medicine Lab, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, 639 Zhizaoju Road, Shanghai 200011, P. R. China.
4. National Center for Translational Medicine, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.

Abstract

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.

Keywords: ROS-sensitive nanoparticles, photodynamic therapy, Camptothecin, UCNPs, orthotopic lung cancer.

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How to cite this article:
Yue C, Zhang C, Alfranca G, Yang Y, Jiang X, Yang Y, Pan F, Fuente JMdl, Cui D. Near-Infrared Light Triggered ROS-activated Theranostic Platform based on Ce6-CPT-UCNPs for Simultaneous Fluorescence Imaging and Chemo-Photodynamic Combined Therapy. Theranostics 2016; 6(4):456-469. doi:10.7150/thno.14101. Available from http://www.thno.org/v06p0456.htm