Engineering Zwitterionic Biomaterials for Immune Modulation and Drug Delivery

Abstract

The development of biotherapeutics, which hold promising potential to treat diverse disease, is limited by their inadequate circulation half-lives and inherent immunogenicity. Conjugation of non-ionic poly (ethylene glycol) (PEG), known as PEGylation, has been widely employed as the gold standard to ameliorate the pharmacokinetic (PK) and immunological profiles of proteins. Unfortunately, PEG grafted onto immunogenic proteins has been shown to induce anti-PEG antibodies (Abs) that could cause loss of efficacy and even lethal adverse reactions. To confront the “PEG dilemma”, zwitterionic materials with superhydrophilicity are emerging as promising alternatives for PEG. This dissertation summarizes recent studies from the design, synthesis and characterization of zwitterionic polymers to the in vitro and in vivo studies of poly(zwitterion)- protein nanomedicine. The influence of PEG and zwitterionic poly(carboxy betaine) (PCB) on immune systems is firstly discussed, revealing the low immunogenic risk of zwitterionic materials. Based on this design principle, new protein-delivery tactics are proposed to avoid the generation of undesirable immune responses, either by completely shielding proteins from immune recognition or by actively inducing antigen-specific immune tolerance. Furthermore, new classes of naturally-inspired inert or immunomodulatory zwitterionic materials are developed to further improve the efficacy and safety of protein therapeutics, enriching the arsenal of biomaterial tools for drug delivery.