title: A photo-activated targeting chemotherapy using glutathione sensitive camptothecin-loaded polymeric micelles.
abstract: OBJECTIVE
  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 (1)H-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.
authors.affiliation: Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Horacio
authors.initials: H
authors.lastname: Cabral
authors.forename: Masataka
authors.initials: M
authors.lastname: Nakanishi
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kumagai
authors.forename: Woo-Dong
authors.initials: WD
authors.lastname: Jang
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishiyama
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka