Functionalizing nanoparticles with cancer-targeting antibodies: A comparison of strategies

Standard cancer therapies sometimes fail to deliver chemotherapeutic drugs to tumor cells in a safe and effective manner. Nanotechnology takes the lead in providing new therapeutic options for cancer due to major potential for selective targeting and controlled drug release. Antibodies and antibody fragments are attracting much attention as a source of targeting ligands to bind specific receptors that are overexpressed on cancer cells. Therefore, researchers are devoting time and effort to develop targeting strategies based on nanoparticles functionalized with antibodies, which hold great promise to enhance therapeutic efficacy and circumvent severe side effects. Several methods have been described to immobilize antibodies on the surface of nanoparticles. However, selecting the most appropriate for each application is challenging but also imperative to preserve antigen binding ability and yield stable antibody-conjugated nanoparticles. From this perspective, we aim to provide considerable knowledge on the most widely used methods of functionalization that can be helpful for decision-making and design of conjugation protocols as well. This review summarizes adsorption, covalent conjugation (carbodiimide, maleimide and "click" chemistries) and biotin-avidin interaction, while discussing the advantages, limitations and relevant therapeutic approaches currently under investigation.