Specific light-up pullulan-based nanoparticles with reduction-triggered emission and activatable photoactivity for the imaging and photodynamic killing of cancer cells.
Activatable photosensitizers that can be activated by cancer-associated stimuli have drawn increasing attention for simultaneous fluorescence imaging and photodynamic ablation of cancer cells. Here, we developed a cancer-cell specific photosensitizer nano-delivery system by synthesizing protoporphyrin IX (PpIX)-conjugated pullulan (P) with reducible disulfide bonds. The amphiphilic P-s-s-PpIX conjugate self-assembled in aqueous condition to form core-shell structured nanoparticles (P-s-s-PpIX NPs) with average size of 166nm, showing reduction-controllable stability. In in vitro, the photoactivity of P-s-s-PpIX NPs in an aqueous environment was significantly suppressed by the self-quenching effect, which kept P-s-s-PpIX NPs in a photo-inactive and quenched state. But in the presence of GSH, P-s-s-PpIX NPs quickly dissociated by reductive breakage of disulfide linkers, followed by the significant recovery of fluorescent emission and singlet oxygen generation. In MCF-7 cells, compared to non-reducible P-PpIX NPs with stable amide linkages, P-s-s-PpIX NPs displayed higher cytotoxicity and induced higher apoptosis rate of tumor cells with light irradiation treatment. As a result, the P-s-s-PpIX NPs may serve as an effective smart nanomedicine platform for specific light-up and reduction-triggered cancer imaging and photodynamic therapy with the prominently reduced damage to normal tissues and cells.
School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, PR China.
Jing
J
Xia
School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, PR China.
Liuwei
L
Zhang
School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, PR China.
Ming
M
Qian
School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, PR China.
Yongming
Y
Bao
State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, PR China; School of Life Science and Biotechnology, Dalian University of Technology, Dalian 116024, PR China. Electronic address: wangjingyun67@dlut.edu.cn.
Jingyun
J
Wang
Department of Environmental Health and Toxicology, School of Public Health, Dalian Medical University, Dalian 116044, PR China. Electronic address: liy76@yahoo.com.
Yachen
Y
Li
D000818:Animals; D017209:Apoptosis; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005453:Fluorescence; D005936:Glucans / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy*; D061848:Optical Imaging / Q000379:methods; D010084:Oxidation-Reduction; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry*; D011524:Protoporphyrins / Q000008:administration & dosage / Q000737:chemistry*; D026082:Singlet Oxygen / Q000737:chemistry; D013499:Surface Properties
D004337:Drug Carriers; D005936:Glucans; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D026082:Singlet Oxygen; C009109:pullulan; C028025:protoporphyrin IX; D005978:Glutathione
Nanoparticle; Photodynamic therapy; Photosensitizer; Pullulan; Self-quenching; Singlet oxygen