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.