Designed Peptide Coacervates for Extracellular Antibody Targeting

Therapeutic antibodies have transformed the treatment of cancer and immune-related diseases. However, improving their stability, protection from degradation, and efficient interaction with target cells remain major challenges. Peptide coacervates, formed by liquid-liquid phase separation (LLPS), are emerging supramolecular assemblies that offer membraneless microenvironments for encapsulation and enrichment of polar macromolecules and thus are especially attractive for delivery applications. Here, we design minimalistic coacervates formed by oppositely charged peptides through LLPS as a functional biomaterial platform for efficient sequestration and extracellular targeting of monoclonal antibodies (mAbs). We use Rituximab (RIT), a human IgG1 mAb targeting CD20 on B cells, widely used in the treatment of B cell malignancies and autoimmune diseases, as a therapeutic mAb model. We show that the coacervates remain stable under physiologically relevant conditions, including serum-containing media and acidic pH, and that they can efficiently encapsulate RIT. Encapsulation within the coacervates enhances antibody-cell interactions and provides partial protection against enzymatic proteolysis, while coacervates maintain low cytotoxicity. Importantly, we demonstrate that the antibody biological activity is preserved by retaining complement-dependent cytotoxicity against CD20-expressing cells. Thus, our findings suggest that encapsulation within the peptide coacervates provides a promising strategy for improving stability, functionality, and extracellular delivery of therapeutic antibodies.