(95c) Biomimetic Peptide-Amphiphiles for Receptor-Targeted Therapeutics

Drug delivery systems that include site-specific surface ligands could further enhance selective targeting. We proposed to enhance selectivity by targeting vesicles (stealth liposomes or polymersomes) to the alpha(5)beta(1) integrin. The alpha(5)beta(1) integrin is an adhesion receptor that is expressed on the cell surface and has been implicated in dynamic processes such as suppressing tumor recurrence and metastasis in certain cases of cancer. Alpha(5)beta(1) is up-regulated by proliferating endothelial cells of the tumor vasculature and also found on different tumors. Colon cancer cells were chosen as the model target system in our study. A fibronectin-mimetic peptide-amphiphile (PR_b) was recently synthesized by our group. Surfaces functionalized with the PR_b sequence were shown to outperform fibronectin covered surfaces (fibronectin is the natural protein ligand for alpha(5)beta(1)) and other peptides in terms of various cellular phenomena, such as cell adhesion, spreading, cytoskeleton formation, and extracellular matrix production (experiments were performed with endothelial cells). The objective of our work is to engineer alpha(5)beta(1)-targeted delivery systems that reach their target and effectively release the encapsulated payload (DNA, chemotherapy agents, or proteins) intracellularly. In this talk I will discuss our results from PR_b-functionalized nanoparticles targeted to colon cancer cells in vitro and in vivo.