title: Dual-effect liposomes encapsulated with doxorubicin and chlorin e6 augment the therapeutic effect of tumor treatment.
abstract: OBJECTIVE
  Long circulating doxorubicin (Dox)-loaded PEGylated liposomes are clinically safer than the free form due to the significant reduction of cardiac toxicity. However, the therapeutic efficacy of the PEGylated liposome could further be improved if poor diffusivity and slow drug release of the liposome in tumor interstitium can be overcome. In this study, a dual-effect liposome triggered by photodynamic effect was developed to improve the therapeutic efficacy of Dox-loaded PEGylated liposomes.
  
  
  METHODS
  Dox and chlorin e6 (Ce6) were co-encapsulated in PEGylated liposomes (named as PL-Dox-Ce6). To induce the drug release, photodynamic effect was triggered by the light irradiation of a 662 nm diode laser. The cellular distribution of Dox and Ce6 was examined under confocal microscope. The in vitro and in vivo cytotoxicity of PL-Dox-Ce6 was determined via the colony formation assay and the synergistic C26 tumor model, respectively.
  
  
  RESULTS
  The cellular distribution of PL-Dox-Ce6 was in the cytoplasmic area; while under light irradiation, Dox was co-localized with nuclear staining positive signals. The cellular cytotoxicity of PL-Dox-Ce6 was significantly higher than the controls including liposomes encapsulating either Dox (PL-Dox) or Ce6 (PL-Ce6). The in vivo treatment efficacy of PL-Dox-Ce6 determined in the C26 tumor model reveals a significant therapeutic effect compared to that of PL-Ce6 and PL-Dox alone or in combination.
  
  
  CONCLUSIONS
  This study indicates that this dual-effect PEGylated liposome could provide clinical advantages in the combination regimen of photodynamic therapy and chemotherapy.
authors.affiliation: Department of Biochemical Science and Technology, National Taiwan University, Taipei, 106, Taiwan.
authors.forename: Po-Chun
authors.initials: PC
authors.lastname: Peng
authors.forename: Ruey-Long
authors.initials: RL
authors.lastname: Hong
authors.forename: Yi-Jane
authors.initials: YJ
authors.lastname: Tsai
authors.forename: Pei-Tzu
authors.initials: PT
authors.lastname: Li
authors.forename: Tsuimin
authors.initials: T
authors.lastname: Tsai
authors.forename: Chin-Tin
authors.initials: CT
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002735:Chlorophyllides; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D054023:Lasers, Semiconductor / Q000627:therapeutic use*; D008081:Liposomes; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D014411:Neoplastic Stem Cells / Q000187:drug effects; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011166:Porphyrins / Q000008:administration & dosage; D011897:Random Allocation; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D002735:Chlorophyllides; D008081:Liposomes; D017319:Photosensitizing Agents; D011166:Porphyrins; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; C062985:phytochlorin; D004317:Doxorubicin
keywords: chemotherapy; photodynamic therapy; photosensitizer