title: 5-aminolevulinic acid-incorporated nanoparticles of methoxy poly(ethylene glycol)-chitosan copolymer for photodynamic therapy.
abstract: OBJECTIVE
  The aim of this study was to make 5-aminolevulinic acid (5-ALA)-incorporated nanoparticles using methoxy polyethylene glycol/chitosan (PEG-Chito) copolymer for application in photodynamic therapy for colon cancer cells.
  
  
  METHODS
  5-ALA-incorporated (PEG-Chito-5-ALA) nanoparticles were prepared by ion complex formation between 5-ALA and chitosan. Protoporphyrin IX accumulation in the tumor cells and phototoxicity induced by PEG-Chito-5-ALA nanoparticles were assessed using CT26 cells in vitro.
  
  
  RESULTS
  PEG-Chito-5-ALA nanoparticles have spherical shapes with sizes diameters 200 nm. More specifically, microscopic observation revealed a core-shell structure of PEG-Chito-5-ALA nanoparticles. 1H NMR spectra showed that 5-ALA was incorporated in the core of the nanoparticles. In the absence of light irradiation, all components such as 5-ALA, empty nanoparticles, and PEG-Chito-5-ALA nanoparticles did not affect the viability of cells. However, 5-ALA or PEG-Chito-5-ALA nanoparticles induced tumor cell death under light irradiation, and the viability of tumor cells was dose-dependently decreased according to the increase in irradiation time. In particular, PEG-Chito-5-ALA nanoparticles induced increased phototoxicity and higher protoporphyrin IX accumulation into the tumor cells than did 5-ALA alone. Furthermore, PEG-Chito-5-ALA nanoparticles accelerated apoptosis/necrosis of tumor cells, compared to 5-ALA alone.
  
  
  CONCLUSIONS
  PEG-Chito-5-ALA nanoparticles showed superior delivery capacity of 5-ALA and phototoxicity against tumor cells. These results show that PEG-Chito-5-ALA nanoparticles are promising candidates for photodynamic therapy of colon cancer cells.
authors.affiliation: National Research and Development Center for Hepatobiliary Disease, Pusan National University Yangsan Hospital, Gyeongnam, Republic of Korea.
authors.forename: Chung-Wook
authors.initials: CW
authors.lastname: Chung
authors.forename: Kyu-Don
authors.initials: KD
authors.lastname: Chung
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Jeong
authors.forename: Dae Hwan
authors.initials: DH
authors.lastname: Kang
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D048271:Chitosan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011524:Protoporphyrins / Q000032:analysis / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D017319:Photosensitizing Agents; D011524:Protoporphyrins; C540518:methoxy poly(ethylene glycol)-grafted chitosan; D011092:Polyethylene Glycols; D000622:Aminolevulinic Acid; D048271:Chitosan; C028025:protoporphyrin IX
keywords: 5-ALA; chitosan; colon cancer; nanoparticles; photosensitizer; protoporphyrin IX