Department of Bioengineering, University of Washington, Seattle, Washington 98195, United States.
Department of Chemical Engineering, University of Washington, Seattle, Washington 98195, United States.
Nano Lett. 2020 Jun 10;20(6):4693-4699. doi: 10.1021/acs.nanolett.0c01713. Epub 2020 May 11.
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.
淋巴系统为许多疾病（如肿瘤转移和病毒感染）的传播提供了主要途径。目前，由于难以将足够的药物输送到淋巴管中，治疗这些疾病仍然是一个棘手的问题。皮下（SC）注射后，药物向淋巴管的转移会因间质空间中的生理屏障而明显减弱。此外，SC 注射对于生物药物来说是一种极具挑战性的给药途径，因为它会增加产生不良免疫反应的风险。在这里，我们通过将蛋白质治疗药物与两性离子聚（羧基甜菜碱）（PCB）聚合物缀合，展示了一种简单有效的策略来解决这一困境。将 PCB 与天冬酰胺酶（ASP）缀合，ASP 是一种高度免疫原性的酶药物，可显著促进 ASP 扩散到淋巴管中，同时减轻其免疫原性。通过实现安全有效的淋巴药物递送，该平台将有助于开发针对各种与淋巴相关疾病的新疗法。
