A photo-activated targeting chemotherapy using glutathione sensitive camptothecin-loaded polymeric micelles

Horacio Cabral, Masataka Nakanishi, Michiaki Kumagai, Woo Dong Jang, Nobuhiro Nishiyama, Kazunori Kataoka

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63 Citations (Scopus)


Purpose. A novel photo-activated targeted chemotherapy was developed by photochemical internalization (PCI) of glutathione-sensitive polymeric micelles incorporating camptothecin (CPT) prepared from thiolated CPT (CPT-DP) and thiolated poly(ethylene glycol)-b-poly(glutamic acid) (PEG-b-P(Glu-DP)) Methods. PEG-b-P(Glu-DP) and CPT-DP were synthesized and characterized by 1H-NMR and gel permeation chromatography, and then mixed to prepare CPT-loaded polymeric micelles (CPT/m). The CPT release from the micelle was studied by reverse phase liquid chromatography. The PCI-activated cytotoxicity of CPT/m against HeLa cells was studied in combination with a non-toxic concentration of dendrimer phthalocyanine-loaded micelles (DPc/m) as the photosensitizer. Results. The diameter of CPT/m was 96 nm and the drug loading was 20% (w/w). CPT was slowly released under the conditions reproducing the extracellular or endosomal environments. However, under the reductive conditions mimicking the cytosol, CPT was rapidly released achieving approximately 90% of the drug release after 24 h. The cytotoxicity of CPT/m was drastically increased on photoirradiation, whereas the CPT/m were not cytotoxic without PCI. Conclusions. The CPT/m released the drug responding to reductive conditions. The PCI-induced endosomal escape exposed CPT/m to the cytosol triggering the drug release. Thus, CPT/m in combination with DPc/m will behave as smart nanocarriers activated only at photoirradiated tissues.

Original languageEnglish
Pages (from-to)82-92
Number of pages11
JournalPharmaceutical Research
Issue number1
Publication statusPublished - 2009 Jan

Bibliographical note

Funding Information:
This research was supported in part by the New Energy and Industrial Technology Development Organization of Japan (project code: P06042), Grant-in-Aid for Cancer Research from the Ministry of Education, Culture, Sports, Science and Technology as well as Grant-in-Aid for Cancer Research and Nanomedicine projects from Ministry of Health, labour and Welfare, Japan.

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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