Monoclonal Antibodies in Nanosystems as a Strategy for Cancer Treatment

Abstract

Monoclonal antibodies (mAbs) are valuable therapeutic tools for targeted therapies to attack tumor cells but preserve healthy tissues, therefore resulting in fewer side effects. With the rise of genetic engineering, recombinant human or humanized mAbs are available in the market for the treatment of cancer, either in monotherapy, in association or conjugated with other drugs. Thus, monovalent or bispecific mAbs find applicability for their antitumor cytotoxic activity, as well as for being able to be used in cancer immunotherapy. Although some antibody-drug conjugates are commercially available, immunoconjugates with nanoparticles are less developed. In this context, nanoparticles play an important role for improving drug delivery, allowing for controlled release and site-specific delivery, both passively, through the enhanced permeation and retention effect, and actively, through the functionalization of nanoparticles with antibodies or antibody fragments with high affinity for receptors overexpressed on tumor cells. The bioconjugation can be performed mainly by adsorption or covalent binding or through the use of adapter molecules. Immobilization of antibodies on the surface of nanoparticles must ensure the desired amount of antibodies per nanoparticle and proper antibody orientation and generate a stable binding in order to preserve its biological activity. In this chapter, the main strategies for conjugating antibodies to nanoparticles through covalent bonds, such as the chemistry of carbodiimide, maleimide, and click, and non-covalent bonds such as adsorption and the biotin-avidin system will be discussed. Herein, we will address the development of monoclonal antibodies, the functionalization strategies, and antibody-receptor-targeted nanoparticles of different compositions, such as lipid, polymeric, and inorganic, focusing on their preparation techniques, physicochemical characterization, and in vitro and in vivo biological activity. Overall, the main bioconjugation technique is provided by the maleimide chemistry, particularly employed in the functionalized of lipid nanoparticles, such as liposomes, the most advanced nanosystem. Cell culture studies have revealed that the functionalized nanoparticle undergoes specific and efficient uptake via receptor-mediated endocytosis. Nanoparticle immunoconjugates have also shown promising for cancer treatment following the success of preclinical studies with cancer xenografts; however, clinical trials have yet to show efficacy and safety.