Zwitterionic peptide pendant as a homing agent to achieve lymphatic targeting antigen-specific immunotherapy of allergenic protein

Targeting the lymphatic route has gained extensive attention in drug delivery due to its potential to reduce drug dosage and improve therapeutic effects. However, the lack of an effective targeting path limits the development of relevant treatments. Herein, we reported a zwitterionic peptide pendant conjugation strategy to render protein drugs with lymphatic targeting capability, which merited subsequent allergen-specific immunotherapy (AIT). The zwitterionic peptide pendant of alternatively repeated glutamic acid (E) and lysine (K) sequences was conjugated to the causative allergenic protein tropomyosin (TM) through recombinant protein expression. The recombinant TM-EK exhibited a decreased immunogenicity and improved lymphatic targeting efficacy. It was found that the TM-EK could effectively induce the mice to achieve immune tolerance to TM and had no noticeable toxic or side effects on major organs. The proposed zwitterionic peptide strategy provided a new approach to developing lymphatic targeting protein drugs and facilitating the improvement of immunotherapies.