Design Rules for Antibody Delivery by Self-Assembled Block-Copolyelectrolyte Nanocapsules br

Monoclonal antibodies (mAbs) are proven bio-pharmaceuticals for the treatment of chronic illnesses, includingcancer, autoimmune, neurodegenerative, and infectious diseases. Afundamental challenge for implementing mAbs in immunotherapyis protecting the protein structure against damage and prolongingits circulation time, which can be achieved using bespoke mAbdelivery systems. One promising class of protein carriers is block-copolyelectrolytes (BCPEs, one natural polyelectrolyte grafted toone neutral hydrophilic polymer block) which self-assemble intostable micelles with a compact core of proteins and charged blockssurrounded 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 proposedmixture of block-copolyanions and block-copolycations naturally promotes encapsulation through balanced physicochemicalinteractions in water and is readily tailorable via molecular engineering of the block-copolyelectrolytes. By developing an integratedcoarse-grained model to screen different copolyelectrolyte carriers for the specific antibody, we map the carrier assembly andencapsulation mechanism of Trastuzumab in water. Our model identifies the parameters that control encapsulation and forecasts theexpectedfinal morphology based on computed phase diagrams of the material over a range of conditions. Specifically forTrastuzumab, we predict that increasing polymer concentration, chain length, and solvent selectivity while decreasing block lengthratio will provide more effective BCPE-based mAb delivery. Our efficient computational model can guide future experiments inoptimizing copolyelectrolyte-based carrier systems for biopharmaceuticals