Nanoparticulate targeted drug delivery using peptides and proteins

: Targeted drug delivery has been widely explored as a strategy to increase drug efficacy and decrease side effects by guiding drugs to a specific location of action. One of the alternatives to promote the active targeting of drugs is to perform surface modification of the drug carrier, in particular nanocarriers, for effective targeted moieties of cells. Peptides, proteins and antibodies have been extensively used as ligands to selectively direct drugs. In particular, these molecules are useful to recognize and bind to target antigens or receptors overexpressed or selectively expressed by particular cells or tissue components. The high specificity is based on the complex, but strong molecular recognition, which is a characteristic of molecules with different interconnection places with targets such as peptides and proteins. For a peptide-based targeting approach it is even more advantageous, because peptides and proteins display high affinities and specificities for other biomolecules. Important requirements for using peptides and proteins as targeting molecules are the ligand that should selectively bind to the cell surface receptors on the targeted cells, the receptor that should be expressed only on the target cells or the expression should be higher in the target cells than in the non-targeted cells, the targeted carrier that should be sufficiently stable in the systemic circulation to reach the target cells at an effective concentration and also the selection of the site of conjugation on the peptide or protein, critical for retaining its binding properties to the receptor, because conjugation may impose a steric hindrance that interferes with receptor recognition. Ideally, conjugation of the drug or carrier to the targeting peptide should not interfere with the recognition of the peptide by its receptor. This chapter aims to present the most recent examples of peptides, proteins and antibodies used in targeted drug delivery, and describe some nanoparticulate delivery systems using peptide and protein surface functionalization as well as current and potential applications of such vectorized systems in pre-clinical and clinical applications.