Tumor-homing photosensitizer-conjugated glycol chitosan nanoparticles for synchronous photodynamic imaging and therapy based on cellular on/off system

So Jin Lee, Heebeom Koo, Dong Eun Lee, Solki Min, Seulki Lee, Xiaoyuan Chen, Yongseok Choi, James F. Leary, Kinam Park, Seo Young Jeong, Ick Chan Kwon, Kwang Meyung Kim, Kuiwon Choi

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4021-4029
Number of pages9
JournalBiomaterials
Volume32
Issue number16
DOIs
Publication statusPublished - 2011 Jun 1

Fingerprint

On-off control systems
Photosensitizing Agents
Photosensitizers
Photochemotherapy
Glycols
Chitosan
Nanoparticles
Tumors
Imaging techniques
Neoplasms
Polymers
Bearings (structural)
Fluorescence
Phototoxic Dermatitis
protoporphyrin IX
glycol-chitosan
Singlet Oxygen
Drug Carriers
Molecules
Oncology

Keywords

  • Cellular on-off system
  • Drug delivery
  • Glycol chitosan
  • Nanoparticle
  • Photodynamic therapy
  • Photosensitizer

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

Tumor-homing photosensitizer-conjugated glycol chitosan nanoparticles for synchronous photodynamic imaging and therapy based on cellular on/off system. / Lee, So Jin; Koo, Heebeom; Lee, Dong Eun; Min, Solki; Lee, Seulki; Chen, Xiaoyuan; Choi, Yongseok; Leary, James F.; Park, Kinam; Jeong, Seo Young; Kwon, Ick Chan; Kim, Kwang Meyung; Choi, Kuiwon.

In: Biomaterials, Vol. 32, No. 16, 01.06.2011, p. 4021-4029.

Research output: Contribution to journalArticle

Lee, So Jin ; Koo, Heebeom ; Lee, Dong Eun ; Min, Solki ; Lee, Seulki ; Chen, Xiaoyuan ; Choi, Yongseok ; Leary, James F. ; Park, Kinam ; Jeong, Seo Young ; Kwon, Ick Chan ; Kim, Kwang Meyung ; Choi, Kuiwon. / Tumor-homing photosensitizer-conjugated glycol chitosan nanoparticles for synchronous photodynamic imaging and therapy based on cellular on/off system. In: Biomaterials. 2011 ; Vol. 32, No. 16. pp. 4021-4029.
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AU - Lee, Seulki

AU - Chen, Xiaoyuan

AU - Choi, Yongseok

AU - Leary, James F.

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AU - Jeong, Seo Young

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AU - Kim, Kwang Meyung

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AB - 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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