Cancer cell-specific photoactivity of pheophorbide a-glycol chitosan nanoparticles for photodynamic therapy in tumor-bearing mice

In hyeok Oh, Hyun Su Min, Li Li, Thanh Huyen Tran, Yong kyu Lee, Ick Chan Kwon, Kuiwon Choi, Kwangmeyung Kim, Kang Moo Huh

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113 Scopus citations

Abstract

We designed a cancer-cell specific photosensitizer nano-carrier by synthesizing pheophorbide a (PheoA) conjugated glycol chitosan (GC) with reducible disulfide bonds (PheoA-ss-GC). The amphiphilic PheoA-ss-GC conjugates self-assembled in aqueous condition to form core-shell structured nanoparticles (PheoA-ss-CNPs) with good colloidal stability and switchable photoactivity. The photoactivity of PheoA-ss-CNPs in an aqueous environment was greatly suppressed by the self-quenching effect, which enabled the PheoA-ss-CNPs to remain photo-inactive and in a quenched state. However, after the cancer cell-specific uptake, the nanoparticular structure instantaneously dissociated by reductive cleavage of the disulfide linkers, followed by an efficient dequenching process. Compared to non-reducible PheoA-conjugated GC-NPs with stable amide linkages (PheoA-CNPs), PheoA-ss-CNPs rapidly restored their photoactivity in response to intracellular reductive conditions, thus presenting higher cytotoxicity with light treatment. In addition, the PheoA-ss-CNPs presented prolonged blood circulation invivo compared to free PheoA, demonstrating enhanced tumor specific targeting behavior through the enhanced permeation and retention (EPR) effect. The enhanced tumor accumulation of PheoA-ss-CNPs enabled tumor therapeutic efficacy that was more efficient than free PheoA in tumor-bearing mice. Based on the enhanced intracellular release for cytosolic high dose and switchable photoactivity mechanism for reduced side effects, these results suggest that PheoA-ss-CNPs have good potential for photodynamic therapy (PDT) in cancer treatment.

Original languageEnglish
Pages (from-to)6454-6463
Number of pages10
JournalBiomaterials
Volume34
Issue number27
DOIs
StatePublished - Sep 2013

Bibliographical note

Funding Information:
This work was financially supported by Basic Science Research Program and the Fusion Technology Project ( 2010-50201 ) through the National Research Foundation of Korea (NRF) , funded by the Ministry of Education, Science and Technology ( 2012005029 ), and by a grant from the Fundamental R&D Program for Core Technology of Materials, funded by the Ministry of Knowledge Economy .

Keywords

  • Cancer-cell specific photoactivity
  • Glycol chitosan nanoparticles
  • Pheophorbide a
  • Photodynamic therapy
  • Switchable photoactivity

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