Targeting Solid Tumors Overexpressing α2β1 Integrin by Self Assembled Nano-carrier

Nano-carriers have been designed to aid the transport of therapeutic agents to tumors to circumvent the problems associated with conventional antitumor drug delivery systems, including their lack of specificity, severe side effects, burst release and damaging the normal cells. Only a few “targeted-nano-carriers” are clinically approved for the delivery of antitumor drugs mainly due to poor availability of selective targeting molecules. Integrins are one of many families of receptors acts as nano-carrier targeting sites. While RGD targeting molecules recognize eight different integrins, the KTR cyclic sequence motif is strictly selective for only α1β1/α2β1 integrins which recognize collagens. This invention describes the synthesis of KTR-cyclic peptidomimetic targeting molecule which is conjugated to a long alkyl group by a poly-ethylene glycol (PEG) linkage allowing the structure to form a self-assembled nano-carrier with hydrophobic core for lipophilic drug encapsulation and α2β1 integrin targeting ability. Nanoparticles were therefore characterized and tested in vitro on three different cell lines for safety and targeting ability. Evaluation of safety showed no harm to cells proliferation ability, no negative effect on both migration and adhesion and the ability to form new vascularization. All of which are important for the distribution of the carrier for minimizing side effect. Integrin α2β1 is highly up regulated to pathological levels on some tumor cells but is present at low physiological levels in resting endothelial cells and most normal organ systems. Therefore, the nano-carrier developed represent a novel drug delivery system (DDS) suitable for diagnosis and drug delivery towards integrin α2β1-targeted cancer therapy.