Integrin alpha(5)beta(1) is expressed on several types of cancer cells, including colon cancer, and play an important role in tumor growth and metastasis. The ability to target the integrin alpha(5)beta(1) using an appropriate drug delivery nanovector can significantly help in inhibiting tumor growth, reducing tumor metastasis, and decreasing deleterious side effects associated with different cancer therapies. Liposomes are nanosized phospholipid bilayer vesicles that have been extensively studied as drug delivery carriers. The goal of this study is to design peptide functionalized stealth liposomes (liposomes covered with polyethylene glycol (PEG)) that will specifically target the integrin alpha(5)beta(1) and effectively release their encapsulated load intracellularly. The PEG provides a steric barrier allowing the liposomes to circulate in the blood and the functionalizing moiety, PR_b peptide, will specifically recognize and bind to alpha(5)beta(1) expressing cells. PR_b is a novel peptide sequence that was designed in our lab and mimics the cell adhesion domain of fibronectin. It includes both RGDSP (the primary recognition site for alpha(5)beta(1)) and PHSRN (the synergy site for alpha(5)beta(1)) connected with a (SG)5 linker. In this study we have demonstrated that by optimizing the amount of PEG and PR_b on the liposomal interface we can engineer nanovectors that bind to mouse and human colon cancer cells in a specific manner and are internalized through alpha(5)beta(1)-mediated endocytosis. GRGDSP-targeted stealth liposomes bind to colon cancer cells and internalize, but they have much lesser efficiency than PR_b targeted stealth liposomes. We have further shown that these liposomes upon internalization are capable of releasing their load intracellularly. The proposed targeted delivery system has a great potential to deliver therapeutic agents directly to colon cancer cells, in an efficient and specific manner.

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