A comparison of peptide and folate receptor targeting of cancer cells: from single agent to nanoparticle

Introduction: There is broad interest in a targeted strategy that delivers a concentrated therapeutic payload to tumor cells, because of the significant potential for improvements in therapeutic outcomes and reduction of side effects if therapeutics can be delivered only to diseased tissue. Areas covered: This review describes how the coupling chemistry and surface charge effects of peptide labeling in nanoparticle drug delivery strategies have proved difficult to control, resulting in many studies that use folate instead. However, the successful peptide targeting of structural, hormonal, cytokine and endocrine receptors in the delivery of therapeutic and diagnostic radionuclides provides a strong indication that it is worth finding methods to synthesize peptide-targeted nanoparticles. Expert opinion: Chemical conjugation to peptides reduces colloidal stability, which is a limiting factor in the development of targeting nanoparticles. Mechanistic studies are needed in order to develop peptide targeting for nanoparticles to rival the selectivity that has been achieved with the small molecule folate. Although most of the work so far has been done using gold nanoparticles, biological and polymer nanoparticles are more colloidally stable and present enormous opportunities for coupling to peptides.