title: Near-infrared light activation of quenched liposomal Ce6 for synergistic cancer phototherapy with effective skin protection.
abstract: Current photodynamic therapy (PDT) is suffering from limited efficacy towards hypoxia tumors and severe post-treatment photo-toxicity such as light-induced skin damages. To make PDT more effective in cancer treatment while being patient-comfortable, herein, a hexylamine conjugated chlorin e6 (hCe6) as the photosensitizer together with a lipophilic near-infrared (NIR) dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR) are co-encapsulated into polyethylene glycol (PEG) shelled liposomes. In the obtained DiR-hCe6-liposome, the photosensitizing effect of hCe6 is quenched by DiR via fluorescence resonance energy transfer (FRET). Interestingly, upon irradiation with a 785-nm NIR laser to photobleach DiR, both fluorescence and photodynamic effect of hCe6 in DiR-hCe6-liposome would be activated. Meanwhile, such NIR irradiation applied on tumors of mice with intravenous injection of DiR-hCe6-liposome could result in mild photothermal heating, which in turn would promote intra-tumor blood flow and relieve tumor hypoxia, contributing to the enhanced photodynamic tumor treatment. Importantly, compared to hCe6-loaded liposomes, DiR-hCe6-liposome without being activated by the 785-nm laser shows much lower skin photo-toxicity, demonstrating its great skin protection effect. This work demonstrates a promising yet simple strategy to prepare NIR-light-activatable photodynamic theranostics for synergistic cancer phototherapy, which is featured high specificity/efficacy in tumor treatment with minimal photo-toxicity towards the skin.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
authors.forename: Liangzhu
authors.initials: L
authors.lastname: Feng
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China.
authors.forename: Danlei
authors.initials: D
authors.lastname: Tao
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China.
authors.forename: Ziliang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chao
authors.affiliation: Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China. Electronic address: zliu@suda.edu.cn.
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China. Electronic address: mwchen@umac.mo.
authors.forename: Meiwan
authors.initials: M
authors.lastname: Chen
mesh_terms: D000818:Animals; D016923:Cell Death; D045744:Cell Line, Tumor; D002735:Chlorophyllides; D004705:Endocytosis; D005260:Female; D007259:Infrared Rays; D008081:Liposomes / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D010789:Phototherapy; D011166:Porphyrins / Q000737:chemistry*; D012867:Skin / Q000528:radiation effects*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D002735:Chlorophyllides; D008081:Liposomes; D011166:Porphyrins; C062985:phytochlorin
keywords: NIR light activatable PDT; Skin protection; Synergistic cancer phototherapy; Tumor reoxygenation