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Targeting VEGF-encapsulated immunoliposomes to MI heart improves vascularity and cardiac function

Robert C. Scott^*, Jenna M. Rosano^*, Zhanna Ivanov^*, Bin Wang, Parkson Lee-Gau Chong, Andrew C. Issekutz^||, Deborah L. Crabbe and Mohammad F. Kiani^*,¶,1

^* Department of Mechanical Engineering and

^¶ Department of Radiation Oncology, Temple University, Philadelphia, Pennsylvania, USA;

Vascular Biology Center, Medical College of Georgia, Augusta, Georgia, USA;

Department of Biochemistry and

Department of Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA; and

^|| Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada

¹ Correspondence: Department of Mechanical Engineering, Temple University, 1947 N. 12th St., Philadelphia, PA 19122, USA. E-mail: mkiani{at}temple.edu

Recent attempts at rebuilding the myocardium using stem cells have yielded disappointing results. The lack of a supporting vasculature may, in part, explain these disappointing findings. However, concerns over possible side effects have hampered attempts at revascularizing the infarcted myocardium using systemic delivery of proangiogenic compounds. In this study, we develop the technology to enhance the morphology and function of postinfarct neovasculature. Previously, we have shown that the up-regulated expression of endothelial cell adhesion molecules in the myocardial infarction (MI) region provides a potential avenue for selectively targeting drugs to infarcted tissue. After treatment with anti-P-selectin-conjugated liposomes containing vascular endothelial growth factor (VEGF), changes in cardiac function and vasculature post-MI were quantified in a rat MI model. Targeted delivery of VEGF to post-MI tissue resulted in significant increase in fractional shortening and improved systolic function. These functional improvements were accompanied by a 21% increase in the number of anatomical vessels and a 74% increase in the number of perfused vessels in the MI region of treated animals. No significant improvements in cardiac function were observed in untreated, systemic VEGF-treated, nontargeted liposome-treated, or blank immunoliposome-treated animals. Targeted delivery of low doses of proangiogenic compounds to post-MI tissue results in significant improvements in cardiac function and vascular structure.—Scott, R. C., Rosano, J. M., Ivanov, Z., Wang, B., Lee-Gau Chong, P., Issekutz, I. C., Crabbe, D. L., Kiani, M. F. Targeting VEGF-encapsulated immunoliposomes to MI heart improves vascularity and cardiac function.

Key Words: adhesion molecules • liposomes • microenvironment • targeted drug delivery

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