Zwitterionic Nanoconjugate Enables Safe and Efficient Lymphatic Drug Delivery

The lymphatic system provides a major route for the dissemination of many diseases such as tumor metastasis and virus infection. At present, treating these diseases remains a knotty task due to the difficulty of delivering sufficient drugs into lymphatics. After subcutaneous (SC) injection, the transferring of drugs to lymphatic vessels is significantly attenuated by physiological barriers in the interstitial space. Moreover, SC injection represents a highly challenging administration route for biological drugs, as it increases the risk of undesirable immune responses. Here, we demonstrate a simple and effective strategy to address this dilemma by conjugating protein therapeutics with zwitterionic poly(carboxy betaine) (PCB) polymers. PCB conjugation to l-asparaginase (ASP), a highly immunogenic enzyme drug, manifests to significantly promote the diffusion of ASP into the lymphatic system while mitigating its immunogenicity. This platform will facilitate the development of new therapies against diverse lymph-related diseases by enabling safe and efficient lymphatic drug delivery.