Design rules for antibody delivery by self-assembled block-copolyelectrolyte nanocapsules

Monoclonal antibodies (mAbs) are proven biopharmaceuticals for the treatment of chronic illnesses, including cancer, autoimmune, neurodegenerative, and infectious diseases. A fundamental challenge for implementing mAbs in immunotherapy is protecting the protein structure against damage and prolonging its circulation time, which can be achieved using bespoke mAb delivery systems. One promising class of protein carriers is block-copolyelectrolytes (BCPEs, one natural polyelectrolyte grafted to one neutral hydrophilic polymer block) which self-assemble into stable micelles with a compact core of proteins and charged blocks surrounded by a corona of neutral blocks. The simple, biocompatible nanocapsule separates the protein from the outer medium. Here, we design a delivery system for Trastuzumab, an immunoglobulin used to treat breast and stomach cancer. Our proposed mixture of block-copolyanions and block-copolycations naturally promotes encapsulation through balanced physicochemical interactions in water and is readily tailorable via molecular engineering of the block-copolyelectrolytes. By developing an integrated coarse-grained model to screen different copolyelectrolyte carriers for the specific antibody, we map the carrier assembly and encapsulation mechanism of Trastuzumab in water. Our model identifies the parameters that control encapsulation and forecasts the expected final morphology based on computed phase diagrams of the material over a range of conditions. Specifically for Trastuzumab, we predict that increasing polymer concentration, chain length, and solvent selectivity while decreasing block length ratio will provide more effective BCPE-based mAb delivery. Our efficient computational model can guide future experiments in optimizing copolyelectrolyte-based carrier systems for biopharmaceuticals.