title: Activatable albumin-photosensitizer nanoassemblies for triple-modal imaging and thermal-modulated photodynamic therapy of cancer.
abstract: Photodynamic therapy (PDT) is a noninvasive and effective approach for cancer treatment. The main bottlenecks of clinical PDT are poor selectivity of photosensitizer and inadequate oxygen supply resulting in serious side effects and low therapeutic efficiency. Herein, a thermal-modulated reactive oxygen species (ROS) strategy using activatable human serum albumin-chlorin e6 nanoassemblies (HSA-Ce6 NAs) for promoting PDT against cancer is developed. Through intermolecular disulfide bond crosslinking and hydrophobic interaction, Ce6 photosensitizer is effectively loaded into the HSA NAs, and the obtained HSA-Ce6 NAs exhibit excellent reduction response, as well as enhanced tumor accumulation and retention. By the precision control of the overall body temperature instead of local tumor temperature increasing from 37 °C to 43 °C, the photosensitization reaction rate of HSA-Ce6 NAs increases 20%, and the oxygen saturation of tumor tissue raise 52%, significantly enhancing the generation of ROS for promoting PDT. Meanwhile, the intrinsic fluorescence and photoacoustic properties, and the chelating characteristic of porphyrin ring can endow the HSA-Ce6 NAs with fluorescence, photoacoustic and magnetic resonance triple-modal imaging functions. Upon irradiation of low-energy near-infrared laser, the tumors are completely suppressed without tumor recurrence and therapy-induced side effects. The robust thermal-modulated ROS strategy combined with albumin-based activatable nanophotosensitizer is highly potential for multi-modal imaging-guided PDT and clinical translation.
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China; Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China.
authors.forename: Dehong
authors.initials: D
authors.lastname: Hu
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China; Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China. Electronic address: zh.sheng@siat.ac.cn.
authors.forename: Zonghai
authors.initials: Z
authors.lastname: Sheng
authors.affiliation: Paul-Drude Institut, Leibniz-Institut im Forschungsverbund, Hausvogteiplatz 5-7, 10117, Berlin, Germany.
authors.forename: Guanhui
authors.initials: G
authors.lastname: Gao
authors.affiliation: Center for High Performance Computing, Institute of Advanced Computing and Digital Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China.
authors.forename: Fungming
authors.initials: F
authors.lastname: Siu
authors.affiliation: Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China.
authors.forename: Chengbo
authors.initials: C
authors.lastname: Liu
authors.affiliation: Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wan
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
authors.affiliation: Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China.
authors.forename: Hairong
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, CAS Key Laboratory of Health Informatics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, PR China. Electronic address: lt.cai@siat.ac.cn.
authors.forename: Lintao
authors.initials: L
authors.lastname: Cai
mesh_terms: D000418:Albumins / Q000737:chemistry*; D000818:Animals; D045744:Cell Line, Tumor; D002735:Chlorophyllides; D004705:Endocytosis; D006801:Humans; D008279:Magnetic Resonance Imaging; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D064847:Multimodal Imaging; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000628:therapy*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D013696:Temperature
chemical_list: D000418:Albumins; D002735:Chlorophyllides; D017319:Photosensitizing Agents; D011166:Porphyrins; D017382:Reactive Oxygen Species; C062985:phytochlorin
keywords: Activatable nanophotosensitizer; Multi-modal imaging; Photodynamic therapy; Theranostics; Thermal modulation