Tumor-homing photosensitizer-conjugated glycol chitosan nanoparticles for synchronous photodynamic imaging and therapy based on cellular on/off system
- Tumor-homing photosensitizer-conjugated glycol chitosan nanoparticles for synchronous photodynamic imaging and therapy based on cellular on/off system
- 이소진; 구희범; 이동은; 민솔기; 이슬기; Xiaoyuan Chen; 최용석; James F. Leary; 박기남; 정서영; 권익찬; 김광명; 최귀원
- Photosensitizer; Nanoparticle; Photodynamic therapy; Drug delivery; Glycol chitosan; Cellular on-off system
- Issue Date
- VOL 32, NO 16, 4021-4029
- Herein, we developed the photosensitizer, protoporphyrin IX (PpIX), conjugated glycol chitosan (GC) nanoparticles (PpIX–GC–NPs) as tumor-homing drug carriers with cellular on/off system for photodynamic imaging and therapy, simultaneously. In order to prepare PpIX–GC–NPs, hydrophobic PpIXs were chemically conjugated to GC polymer and the amphiphilic PpIX–GC conjugates formed a stable nanoparticle structure in aqueous condition, wherein conjugated PpIX molecules formed hydrophobic inner-cores and they were covered by the hydrophilic GC polymer shell. Based on the nanoparticle structure, PpIX–GC–NPs showed the self-quenching effect that is ‘off’ state with no fluorescence signal and phototoxicity with light exposure. It is due to the compact crystallized PpIX molecules in the nanoparticles as confirmed by dynamic light scattering and X-ray diffraction methods. However, after cellular uptake, compact nanoparticle structure gradually decreased to generate strong fluorescence signal and singlet oxygen generation when irradiated. Importantly, PpIX–GC–NPs-treated mice presented prolonged blood circulation, enhanced tumor targeting ability, and improved in vivo therapeutic efficiency in tumor-bearing mice, compared to that of free PpIX-treated mice. These results proved that this tumor-homing cellular ‘on/off’ nanoparticle system of PpIX–GC–NPs has a great potential for synchronous photodynamic imaging and therapy in cancer treatment.
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