Engineering Zwitterionic-switchable Chromatin-mimetic Nanoparticles for Immune Modulation
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Currently, one of the major obstacles that impede the wide application of therapeutic protein products is their potential immunogenicity, especially for those obtained from non-human sources. The immune response will decrease the efficacy of protein drugs and lead to adverse events such as anaphylaxis, cytokine-release syndrome, and cross-reactive neutralization of endogenous proteins. This thesis studied an immunosuppressive nanoparticle capable of inducing durable immune tolerance to co-delivered proteins in order to suppress the unwanted immune responses against protein drugs. The formulation of this nanoparticle was developed and optimized to stably encapsulate protein antigens and immunosuppressive nucleotides simultaneously. The stability and degradability of this nanoparticle were also characterized. Moreover, using KLH as a model protein antigen, we demonstrated that the immunosuppressive nanoparticle in mice could mitigate the immune responses against KLH. Collectively, the immunosuppressive nanoparticle developed in this thesis provides a general tool to decrease undesirable immune responses.
- Bioengineering