title: pH-Sensitive self-assembling nanoparticles for tumor near-infrared fluorescence imaging and chemo-photodynamic combination therapy.
abstract: The development of visual tumor theranostic nanoparticles has become a great challenge. In this study, d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was conjugated to acid-sensitive cis-aconitic anhydride-modified doxorubicin (CAD) to obtain pH-sensitive anti-tumor prodrug nanoparticles (TCAD NPs) via self-assembling. Subsequently, the photosensitizer chlorin e6 (Ce6) was loaded into the resulting prodrug nanoparticles to prepare a novel tumor near-infrared fluorescence imaging and chemo-photodynamic combination therapy system (TCAD@Ce6 NPs). An accelerated release of doxorubicin (DOX) and chlorin e6 (Ce6) from the TCAD@Ce6 NPs could be achieved due to the hydrolysis of the acid-sensitive amide linker under mild acidic conditions (pH = 5.5). An in vitro experiment showed that A549 lung cancer cells exhibited a significantly higher uptake of DOX and Ce6 by using our delivery system than the free form of DOX and Ce6. An in vivo experiment showed that TCAD@Ce6 NPs displayed better tumor targeting gathering through the enhanced permeability and retention (EPR) effect than free Ce6, thus improving fluorescence imaging. Moreover, the chemo-photodynamic combination therapy of TCAD@Ce6 NPs combined with near-infrared laser irradiation was confirmed to be capable of inducing high apoptosis and necrosis of tumor cells (A549) in vitro and to display a significantly higher tumor growth suppression in the A549 lung cancer-bearing mice model. Furthermore, compared with exclusive chemotreatment (DOX) or photodynamic treatment (Ce6), our system showed enhanced therapeutic effects both in vitro and in vivo. In conclusion, the high performance TCAD@Ce6 NPs can be used as a promising NIR fluorescence imaging and highly effective chemo-photodynamic system for theranostics of lung cancer, etc. in the near future.
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P.R. China. yumingyang@sjtu.edu.cn dxcui@sjtu.edu.cn and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Wenxiu
authors.initials: W
authors.lastname: Hou
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P.R. China. yumingyang@sjtu.edu.cn dxcui@sjtu.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P.R. China. yumingyang@sjtu.edu.cn dxcui@sjtu.edu.cn and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P.R. China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Qian
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P.R. China. yumingyang@sjtu.edu.cn dxcui@sjtu.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Pan
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P.R. China. yumingyang@sjtu.edu.cn dxcui@sjtu.edu.cn.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P.R. China. yumingyang@sjtu.edu.cn dxcui@sjtu.edu.cn.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P.R. China. yumingyang@sjtu.edu.cn dxcui@sjtu.edu.cn and Instituto de Nanociencia de Aragón, Universidad de Zaragoza, Spain.
authors.forename: Jesús Martínez
authors.initials: JM
authors.lastname: de la Fuente
authors.affiliation: Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, P.R. China. yumingyang@sjtu.edu.cn dxcui@sjtu.edu.cn.
authors.forename: Daxiang
authors.initials: D
authors.lastname: Cui
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002735:Chlorophyllides; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D061848:Optical Imaging / Q000379:methods*; D010778:Photochemotherapy / Q000379:methods*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D011166:Porphyrins / Q000737:chemistry / Q000494:pharmacology; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D002735:Chlorophyllides; D011166:Porphyrins; D014810:Vitamin E; D011092:Polyethylene Glycols; C062985:phytochlorin; D004317:Doxorubicin; C014225:tocophersolan