(23h) Surface-Functionalized Calcium Phosphate Nanoparticles for Selective Cancer Cell Targeting

Over the past few decades, rapid growth of nanotechnology has addressed major challenges that traditional technologies cannot sufficiently address. Nanomedicine has shown promising results in disease treatment and nanoparticles have attracted interest in the medical field as effective carriers for drug delivery. Particularly for cancer, which is one of the most lethal diseases throughout the world, the employment of nanoparticles as drug carriers is a rapidly evolving strategy to overcome the difficulties in therapeutic delivery to the tumor site [1]. Due to their high surface-to-volume ratio (large surface area/small size) and tunable surface chemistry, nanoparticulate carriers present novel properties compared to their bulk counterparts and these properties are harnessed to achieve specific advantages, such as high drug loading, controlled drug release, low toxicity, tissue targeting, long circulation time etc.

In this regard, here we present an approach utilizing nanoparticle delivery of chemotherapeutic drugs to tumor cells. We fabricate and characterize a delivery system based on calcium phosphate (CaP) nanoparticles as the carriers, epidermal growth factor (EGFR) antibodies as targeting agents and doxorubicin (DOX) as an anticancer drug. CaP nanoparticles are synthesized by flame spray pyrolysis [2]. Calcium phosphates represent an important family of biomaterials in drug delivery because of their excellent biocompatibility, low toxicity and non-immunogenicity. Upon their synthesis, their surface is modified by polyethylene glycol (PEG) with carboxyl- and amine-terminated functional groups. The ligand density is optimized along with the dispersion protocol before and after functionalization, in order to have suitable hydrodynamic sizes and ensure long circulation times, effective transport across the tumor vessels and deep penetration into the tumor. The functional end-groups of the ligands are then linked with anti-EGFR antibody to enhance tumor specificity. Finally, DOX is incorporated in the nanoconjugates. The cytotoxicity of these nanocarriers on lung epithelial cells is evaluated in vitro.

This strategy could be used as a generalized therapeutic treatment for a variety of cancers characterized by overexpression of EGFR.