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.