10.1021/acsnano.8b04314.s001 Bowen Li Bowen Li Zhefan Yuan Zhefan Yuan Patrick McMullen Patrick McMullen Jingyi Xie Jingyi Xie Priyesh Jain Priyesh Jain Hsiang-Chieh Hung Hsiang-Chieh Hung Shihan Xu Shihan Xu Peng Zhang Peng Zhang Xiaojie Lin Xiaojie Lin Kan Wu Kan Wu Shaoyi Jiang Shaoyi Jiang A Chromatin-Mimetic Nanomedicine for Therapeutic Tolerance Induction American Chemical Society 2018 Chromatin-Mimetic Nanomedicine proof-of-concept study keyhole limpet hemocyanin prophylactic treatments asthma murine model immunogenic model protein tolerance induction tolerogenic function protein cargos Therapeutic Tolerance Induction airway inflammation KLH response chromatin-mimetic nanomedicine nature-inspired concept PEGylated uricase OVA 2018-11-09 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/A_Chromatin-Mimetic_Nanomedicine_for_Therapeutic_Tolerance_Induction/7352723 The undesirable immune response poses a life-threatening challenge to human health. It not only deteriorates the therapeutic performance of biologic drugs but also contributes to various diseases such as allergies and autoimmune diseases. Inspired by the role of chromatin in the maintenance of natural immune tolerance, here we report a DNA-protein polymeric nanocomplex that can mimic the tolerogenic function of chromatin and induce an immune tolerance to its protein cargos. We first proved that the chromatin-mimetic nanomedicine loaded with keyhole limpet hemocyanin (KLH), a highly immunogenic model protein, could elicit a durable antigen-specific immune tolerance to KLH lasting for at least five weeks in mice. Following the proof-of-concept study, we demonstrated that this nanomedicine could be applied to improve the safety and efficacy of a biologic drug, PEGylated uricase, by attenuating the relevant antibody (Ab) responses. Moreover, we also demonstrated that prophylactic treatments with this nanomedicine could tolerize the immune system with the allergen of ovalbumin (OVA) and thus inhibit the occurrence of airway inflammation in an OVA-induced allergic asthma murine model. Collectively, our work illustrates a nature-inspired concept of immune tolerance induction and establishes a useful tool to specifically suppress unwanted immune responses for therapeutic purposes.