title: PEGylated nanoliposomes encapsulating angiogenic peptides improve perfusion defects: Radionuclide imaging-based study.
abstract: Although liposomes hold promise for cancer therapy, the effectiveness of treating myocardial ischemia by promoting angiogenesis has yet to be proved. Nanoliposomes loaded with therapeutic agents can effectively target ischemic myocardium via enhanced permeability and retention. Surface polyethylene glycol (PEG) modification can further facilitate effective targeting by prolonging liposomal circulation. This study aimed to determine whether PEGylated nanoliposomes are effective in facilitating targeted drug delivery and treating myocardial ischemia.
  
  
  
  Rats subjected to 30min of myocardial ischemia were given (99m)Tc-hexamethylpropyleneamine oxime- or (99m)Tc-diethylenetriamine pentaacetate-labeled liposomes with mean diameters of ~100nm or ~600nm with or without PEG modifications to determine the extent of myocardial uptake in the different conditions. Therapeutic effectiveness was assessed by studying changes in myocardial perfusion defects with (99m)Tc-tetrofosmin autoradiography and vascular density with immunohistochemistry at 7days post-treatment.
  
  
  
  The liver and spleen showed the largest capacity for liposome uptake. Uptake by the liver and spleen was more pronounced when the liposomes were larger. Conversely, myocardial liposome uptake was significantly greater when the liposomes were ~100nm rather than ~600nm in diameter. Surface modification with PEG significantly augmented myocardial uptake of ~100nm liposomes. PEG modification did not affect the size dependence. To investigate therapeutic efficacy, hearts subjected to ischemia received PEGylated nanoliposomes encapsulated with angiogenic peptides. Our data demonstrated that PEGylated nanoliposomes loaded with angiogenic peptides improved myocardial perfusion defects and increased vascular density. A 10-fold increase in liposomal concentration did not further benefit myocardial ischemia.
  
  
  
  Liposomal angiogenic formulation with size control and PEG modification may be effective treatment strategy for myocardial ischemia. Increasing the concentration of liposomes does not necessarily benefit myocardial ischemia.
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging and Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea.
authors.forename: Hyosook
authors.initials: H
authors.lastname: Hwang
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging and Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea.
authors.forename: Hwan-Seok
authors.initials: HS
authors.lastname: Jeong
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging and Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea.
authors.forename: Phil-Sun
authors.initials: PS
authors.lastname: Oh
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging and Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea.
authors.forename: Minjoo
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging and Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea.
authors.forename: Tai-Kyoung
authors.initials: TK
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging and Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea.
authors.forename: JeongIl
authors.initials: J
authors.lastname: Kwon
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging and Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea.
authors.forename: Hyeon-Soo
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging and Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea.
authors.forename: Seok Tae
authors.initials: ST
authors.lastname: Lim
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging and Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea.
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Sohn
authors.affiliation: Department of Nuclear Medicine, Molecular Imaging and Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Sciences, Biomedical Research Institute, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea. Electronic address: jayjeong@jbnu.ac.kr.
authors.forename: Hwan-Jeong
authors.initials: HJ
authors.lastname: Jeong
mesh_terms: D042501:Angiogenic Proteins / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002214:Capsules; D003326:Coronary Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008081:Liposomes; D008297:Male; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000378:metabolism / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000378:metabolism / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry*; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D042501:Angiogenic Proteins; D002214:Capsules; D008081:Liposomes; D009943:Organophosphorus Compounds; D015609:Organotechnetium Compounds; D011092:Polyethylene Glycols; C078700:technetium tc-99m tetrofosmin
keywords: (99m)Tc gamma imaging; Liposomes; Myocardial ischemia; Nuclear imaging; PEGylation