PURPOSE: 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.
PURPOSE: 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 hepatomarats, 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: K Berg; P K Selbo; A Weyergang; A Dietze; L Prasmickaite; A Bonsted; B Ø Engesaeter; E Angell-Petersen; T Warloe; N Frandsen; A Høgset Journal: J Microsc Date: 2005-05 Impact factor: 1.758
Authors: Tricia J Vos; Andrei Caracoti; Jennifer L Che; Mingshi Dai; Cheryl A Farrer; Nancy E Forsyth; Stacey V Drabic; Robert A Horlick; Diana Lamppu; David L Yowe; Suresh Balani; Ping Li; Hang Zeng; Ingrid B J K Joseph; Luis E Rodriguez; Martin P Maguire; Michael A Patane; Christopher F Claiborne Journal: J Med Chem Date: 2004-03-25 Impact factor: 7.446