title: Novel methods to incorporate photosensitizers into nanocarriers for cancer treatment by photodynamic therapy.
abstract: OBJECTIVE
  A hydrophobic photosensitizer, 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH), was loaded into nontoxic biodegradable amine functionalized polyacrylamide (AFPAA) nanoparticles using three different methods (encapsulation, conjugation, and post-loading), forming a stable aqueous dispersion. Each formulation was characterized for physicochemical properties as well as for photodynamic performance so as to determine the most effective nanocarrier formulation containing HPPH for photodynamic therapy (PDT).
  
  
  METHODS
  HPPH or HPPH-linked acrylamide was added into monomer mixture and polymerized in a microemulsion for encapsulation and conjugation, respectively. For post-loading, HPPH was added to an aqueous suspension of pre-formed nanoparticles. Those nanoparticles were tested for optical characteristics, dye loading, dye leaching, particle size, singlet oxygen production, dark toxicity, in vitro photodynamic cell killing, whole body fluorescence imaging and in vivo PDT.
  
  
  RESULTS
  HPPH was successfully encapsulated, conjugated or post-loaded into the AFPAA nanoparticles. The resultant nanoparticles were spherical with a mean diameter of 29 ± 3 nm. The HPPH remained intact after entrapment and the HPPH leaching out of nanoparticles was negligible for all three formulations. The highest singlet oxygen production was achieved by the post-loaded formulation, which caused the highest phototoxicity in in vitro assays. No dark toxicity was observed. Post-loaded HPPH AFPAA nanoparticles were localized to tumors in a mouse colon carcinoma model, enabling fluorescence imaging, and producing a similar photodynamic tumor response to that of free HPPH in equivalent dose.
  
  
  CONCLUSIONS
  Post-loading is the promising method for loading nanoparticles with hydrophobic photosensitizers to achieve effective in vitro and in vivo PDT.
authors: Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors: Shouyan
authors: S
authors: Wang
authors: Wenzhe
authors: W
authors: Fan
authors: Gwangseong
authors: G
authors: Kim
authors: Hoe Jin
authors: HJ
authors: Hah
authors: Yong-Eun Koo
authors: YE
authors: Lee
authors: Raoul
authors: R
authors: Kopelman
authors: Manivannan
authors: M
authors: Ethirajan
authors: Anurag
authors: A
authors: Gupta
authors: Lalit N
authors: LN
authors: Goswami
authors: Paula
authors: P
authors: Pera
authors: Janet
authors: J
authors: Morgan
authors: Ravindra K
authors: RK
authors: Pandey
mesh_terms: D000180:Acrylic Resins / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D045744:Cell Line, Tumor; D002734:Chlorophyll / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D002734:Chlorophyll; D004337:Drug Carriers; D017319:Photosensitizing Agents; D000099166:Polyacrylamides; C083998:2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a