Antibody Nanocarriers for Cancer Management

Abstract

Antibodies are extremely valuable tools in modern medicine due to their ability to target diseased cells through selective antigen binding and thereby regulate cellular signaling or inhibit cell-cell interactions with high specificity. However, the therapeutic utility of freely delivered antibodies is limited by high production costs, low efficacy, dose-limiting toxicities, and inability to cross the cellular membrane (which hinders antibodies against intracellular targets). To overcome these limitations, researchers have begun to develop nanocarriers that can improve antibodies' delivery efficiency, safety profile, and clinical potential. This review summarizes recent advances in the design and implementation of nanocarriers for extracellular or intracellular antibody delivery, emphasizing important design considerations, and points to future directions for the field.

Keywords: binding affinity; multivalency; nanoparticles; signal cascade interference; targeted antibodies.

Figure 1.. Overview of antibody therapeutics.

(A) FDA approved antibodies per year. The number of antibody therapeutics approved yearly has grown at almost an exponential rate over the last two decades. (B) Antibody structure. Antibodies contain unique structural components, including the Fab region that defines antigen-specific binding. Portions of this figure were produced using Servier Medical Art templates (https://smart.servier.com). Servier Medical Art by Servier is licensed under a Creative Commons Attribution 4.0 Unported License.

Figure 2.. Comparison of antibody nanocarriers and freely delivered antibodies for extracellular receptor targeting and ligand blockade.

(Left) When extracellular ligands bind receptors that are overexpressed on diseased cells, intracellular signaling cascades that promote disease progression are activated. (Center) When freely delivered antibodies compete with the ligands for receptor binding sites, intracellular signaling is reduced. (Right) Antibody nanocarriers can engage multiple receptors simultaneously, and this multivalent binding leads to increased binding strength and greater signaling inhibition than is achieved by freely delivered antibodies. Portions of this figure were produced using Servier Medical Art templates (https://smart.servier.com). Servier Medical Art by Servier is licensed under a Creative Commons Attribution 4.0 Unported License.

Figure 3.. Schematic illustration of dual complementary liposome (DCL) structure and mechanisms of action.

(A) Scheme showing the structure of a DCL. (B) DCLs exhibit enhanced cellular binding owing to precisely matched, multivalent ligand-receptor interactions. (C) DCL internalization is enhanced through the cooperative ICAM1 and EGFR endocytosis pathways. (D) DCLs synergistically block the ICAM1 and EGFR signaling cascades to improve therapeutic efficacy. This figure is reproduced with permission from “Dual complementary liposomes inhibit triple-negative breast tumor progression and metastasis” by Guo P, et al. (DOI: 10.1126/sciadv.aav5010). The original article published in Science Advances (https://advances.sciencemag.org/) is licensed under a Creative Commons Attribution 4.0 Unported License.

Figure 4.. Intracellular delivery of antibodies via nanocarriers.

Antibody nanocarriers have been designed to overcome the cellular and endosomal membrane barriers to allow therapeutic antibodies to bind and inhibit targeted proteins intracellularly. Portions of this figure were made using Servier Medical Art templates (https://smart.servier.com). Servier Medical Art by Servier is licensed under a Creative Commons Attribution 4.0 Unported License.