Glypican-1 nanoliposomes for potentiating growth factor activity in therapeutic angiogenesis

详细信息    查看全文

• 作者：Anthony J. Monteforte^a ; Brian Lam^a ; Subhamoy Das^a ; Somshuvra Mukhopadhyay^b ; ^c ; ^d ; Catherine S. Wright^e ; Patricia E. Martin^e ; Andrew K. Dunn^a ; Aaron B. Baker^a ; ^d ; ^f ; ^g ; ^{abbaker@austin.utexas.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Angiogenesis ; Neovascularization ; Ischemia ; Fibroblast growth factor-2 (FGF-2) ; Vascular endothelial growth factor (VEGF) ; Glypican-1 ; Proteoliposomes ; Peripheral arterial disease
• 刊名：Biomaterials
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：94
• 期：Complete
• 页码：45-56
• 全文大小：4352 K

文摘

Therapeutic angiogenesis is a highly appealing concept for treating tissues that become ischemic due to vascular disease. A major barrier to the clinical translation of angiogenic therapies is that the patients that are in the greatest need of these treatments often have long term disease states and co-morbidities, such as diabetes and obesity, that make them resistant to angiogenic stimuli. In this study, we identified that human patients with type 2 diabetes have reduced levels of glypican-1 in the blood vessels of their skin. The lack of this key co-receptor in the tissue may make the application of exogenous angiogenic growth factors or cell therapies ineffective. We created a novel therapeutic enhancer for growth factor activity consisting of glypican-1 delivered in a nanoliposomal carrier (a “glypisome”). Here, we demonstrate that glypisomes enhance FGF-2 mediated endothelial cell proliferation, migration and tube formation. In addition, glypisomes enhance FGF-2 trafficking by increasing both uptake and endosomal processing. We encapsulated FGF-2 or FGF-2 with glypisomes in alginate beads and used these to deliver localized growth factor therapy in a murine hind limb ischemia model. Co-delivery of glypisomes with FGF-2 markedly increased the recovery of perfusion and vessel formation in ischemic hind limbs of wild type and diabetic mice in comparison to mice treated with FGF-2 alone. Together, our findings support that glypisomes are effective means for enhancing growth factor activity and may improve the response to local angiogenic growth factor therapies for ischemia.