Development of a Targeted Drug Delivery System: Monoclonal Antibodies Adsorption onto Bonelike Hydroxyapatite Nanocrystal Surface

Abstract

Together with cancer biomarker advance, nanotechnology could lead to a “personalized oncology”, where early tumour detection and diagnosis are more and more specific. A nanosized drug delivery system is mainly composed of three fundamental elements: i) a drug nanocarrier (1-100 nm), ii) an anti-cancer drug; iii) an active targeting molecule, recognizing a tumour associated marker expressed at the cell surface. In our study we used: i) hydroxyapatite nanocrystals (HA-NC), for its properties of large specific surface area, hydrophilicity and biodegradability with very low toxicity and ii) monoclonal antibodies (mAb), directed against CAR-3, a mucin tumour associated surface antigen, and against the Met/HGF-R, both of which are overexpressed on human carcinomas. In our study, nanosized HA-NC, poorly aggregating and biomimetic, were synthetised and characterized. After a preliminary isothermal adsorption of human polyclonal IgG, we functionalized HA-NC, coated or not with protein A (Prot A), with the two mAbs. IgG and Prot A isothermal adsorption curves were obtained; mAb absorption was achieved and prelimary Prot A coating appeared not to improve HA-NC loading capacity. IgG conformation onto HA-NC was investigated by means of Fourier Transformed InfraRed Spectroscopy, revealing a preferential binding with the constant antibody domain, and exposition of the variable domain, involved in antigen binding, on the biomaterial surface. These immunocomplexes are confirmed to be potentially used as targeted drug delivery system.