Calcium phosphate nanoparticles: second-generation nonviral vectors in gene therapy

Adverse effects of viral vectors, instability of naked DNA, cytotoxicity and low transfection of cationic lipids, cationic polymers and other synthetic vectors are currently severe limitations in gene therapy. In addition to targeting a specific cell type, an ideal nonviral vector must manifest an efficient endosomal escape, render sufficient protection of DNA in the cytosol and help provide an easy passage of cytosolic DNA to the nucleus. Virus-like size calcium phosphate nanoparticles have been found to overcome many of these limitations in delivering genes to the nucleus of specific cells. This review has focused on some applications of DNA-loaded calcium phosphate nanoparticles as nonviral vectors in gene delivery, and their potential use in gene therapy, as well as highlighting the mechanistic studies to probe the reason for high transfection efficiency of the vector. It has been demonstrated that calcium ions play an important role in endosomal escape, cytosolic stability and enhanced nuclear uptake of DNA through nuclear pore complexes. The special role of exogenous calcium ions to overcome obstacles in practical realization of this field suggests that calcium phosphate nanoparticles are not 'me too' synthetic vectors and can be designated as second-generation nonviral vectors for gene therapy.