title: Liver cancer targeting of Doxorubicin with reduced distribution to the heart using hematoporphyrin-modified albumin nanoparticles in rats.
abstract: OBJECTIVE
  To evaluate the usefulness of hematoporphyrin (HP)-modification of the surface of doxorubicin (DOX)-loaded bovine serum albumin (BSA) nanoparticles (NPs) in the liver cancer-selective delivery of DOX.
  
  
  METHODS
  HP-modified NPs (HP-NPs) were prepared by conjugation of amino groups on the surface of NPs with HP, a ligand for low density lipoprotein (LDL) receptors on the hepatoma cells. In vitro cellular accumulation of DOX, in vivo biodistribution of DOX, safety, and anti-tumor efficacy were evaluated for HP-NPs.
  
  
  RESULTS
  Cytotoxicity and accumulation of DOX were in the order of HP-NPs>NPs>solution form (SOL). Cellular uptake from HP-NPs was proportional to the expression level of LDL receptors on the cells, indicating possible involvement of LDL receptor-mediated endocytosis (RME) in uptake. The "merit index," an AUC ratio of DOX in liver (target organ) to DOX in heart (major side effect organ) following iv administration of HP-NPs to hepatoma rats, was 132.5 and 4 times greater compared to SOL and NPs, respectively. The greatest suppression of body weight decrease and tumor size increase was observed for iv-administered HP-NPs in tumor-bearing mice.
  
  
  CONCLUSIONS
  HP modification appears to be useful in selective delivery of NP-loaded DOX to tumors.
authors.affiliation: National Research Laboratory for Transporters Targeted Drug Design Research Institute of Pharmaceutical Sciences College of Pharmacy, Seoul National University, Seoul, 151-742, South Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Chang
authors.forename: Won-Sik
authors.initials: WS
authors.lastname: Shim
authors.forename: Su-Geun
authors.initials: SG
authors.lastname: Yang
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kwak
authors.forename: Saeho
authors.initials: S
authors.lastname: Chong
authors.forename: Dae-Duk
authors.initials: DD
authors.lastname: Kim
authors.forename: Suk-Jae
authors.initials: SJ
authors.lastname: Chung
authors.forename: Chang-Koo
authors.initials: CK
authors.lastname: Shim
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D002417:Cattle; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000379:methods; D006415:Hematoporphyrins / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009206:Myocardium / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000737:chemistry*
chemical_list: D000903:Antibiotics, Antineoplastic; D006415:Hematoporphyrins; D012710:Serum Albumin, Bovine; D004317:Doxorubicin