title: A comparative study between nanoparticle-targeted therapeutics and bioconjugates as obesity medication.
abstract: Antiangiogenesis has been the focus of a new strategy for the treatment of obesity. However, little is known regarding the issue of whether targeting angiogenesis by nanoparticle-targeted therapeutic is advantageous or not in debugging the co-morbidity associated with diet-induced obesity (DIO) and the metabolic syndrome. We report herein on the positive effect of prohibitin (an adipose vascular marker)-targeted nanoparticle (PTNP) encapsulated in a proapoptotic peptide [(D)(KLAKLAK)₂, KLA] on DIO and dysfunctional adipose tissue, a major mediator of the metabolic syndrome, as evidenced by ectopic fat deposition. The systemic injection of DIO mice with a low dose of KLA-PTNP, rather than a bioconjugate composed of the same targeting peptide and KLA (Adipotide) resulted in a reduction in body weight, as evidenced by a significant decrease in serum leptin levels, in parallel with an antiobesity effect on dysfunctional adipose cells, including adipocytes and macrophages. In addition, the KLA-PTNP treatment resulted in a reduction in ectopic fat deposits in liver and muscle with the lipolytic action of elevated serum adiponectin, with no detectable hepatoxicity. Notably, drug delivery via PTNP that had accumulated in obese fat via the enhanced permeability and retention effect was enhanced by multivalent active targeting and cytoplasmic delivery into adipose endothelial cells via escaping from endosomes/lysosomes. Thus, vascular-targeted nanotherapy has the potential to contribute to the control of adipose function and ectopic fat deposition associated with obesity and the metabolic syndrome.
authors.affiliation: Laboratory of Innovative Nanomedicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12, Nishi 6, Kita-ku, Sapporo, Hokkaido 060-0812, Japan.
authors.forename: Nazir
authors.initials: N
authors.lastname: Hossen
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Kajimoto
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Akita
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hyodo
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles / Q000627:therapeutic use*; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D010455:Peptides / Q000627:therapeutic use*; D057786:Peptidomimetics / Q000627:therapeutic use*; D000091402:Prohibitins; D012097:Repressor Proteins
chemical_list: D052242:Adiponectin; D019440:Anti-Obesity Agents; C576018:CKGGRAKDC-GG-D(KLAKLAK)2; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D010455:Peptides; D057786:Peptidomimetics; D000091402:Prohibitins; D012097:Repressor Proteins
keywords: Adipotide; Antiangiogenesis; Diet-induced obesity; Ectopic fat; Metabolic syndrome; Nanoparticle-targeted proapoptotic peptide