title: Near-Infrared Light Triggered ROS-activated Theranostic Platform based on Ce6-CPT-UCNPs for Simultaneous Fluorescence Imaging and Chemo-Photodynamic Combined Therapy.
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.
authors.affiliation: 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;
authors.forename: Caixia
authors.initials: C
authors.lastname: Yue
authors.affiliation: 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;
authors.forename: Chunlei
authors.initials: C
authors.lastname: Zhang
authors.affiliation: 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;
authors.forename: Gabriel
authors.initials: G
authors.lastname: Alfranca
authors.affiliation: 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;
authors.forename: Yao
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Xinquan
authors.initials: X
authors.lastname: Jiang
authors.affiliation: 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;
authors.forename: Yuming
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 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;
authors.forename: Fei
authors.initials: F
authors.lastname: Pan
authors.affiliation: 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;
authors.forename: Jesús M
authors.initials: JM
authors.lastname: de la Fuente
authors.affiliation: 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;; 4. National Center for Translational Medicine, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.
authors.forename: Daxiang
authors.initials: D
authors.lastname: Cui
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics; D002166:Camptothecin / Q000008:administration & dosage / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002735:Chlorophyllides; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000528:radiation effects*; D004358:Drug Therapy / Q000379:methods*; D006801:Humans; D007259:Infrared Rays; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism; D061848:Optical Imaging / Q000379:methods*; D010778:Photochemotherapy / Q000379:methods*; D011166:Porphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000068936:Theranostic Nanomedicine / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002735:Chlorophyllides; D004337:Drug Carriers; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; D017382:Reactive Oxygen Species; C062985:phytochlorin; D002166:Camptothecin
keywords: Camptothecin; ROS-sensitive nanoparticles; UCNPs; orthotopic lung cancer.; photodynamic therapy