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用于胰岛表面修饰和免疫反应抑制的聚乙二醇树枝状大分子的合成。

Synthesis of PEG-dendron for surface modification of pancreatic islets and suppression of the immune response.

作者信息

Jeon Seong Ik, Jeong Jee-Heon, Kim Ju Eun, Haque Muhammad R, Kim Jungahn, Byun Youngro, Ahn Cheol-Hee

机构信息

Research Institute of Advanced Materials (RIAM), Department of Materials Science and Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea.

出版信息

J Mater Chem B. 2021 Mar 21;9(11):2631-2640. doi: 10.1039/d1tb00069a. Epub 2021 Mar 8.

Abstract

Islet cell transplantation has been an effective method for the treatment of type 1 diabetes. The transplanted islets release insulin in response to changes in blood glucose levels. The clinical application of islet transplantation, however, has been hindered because of some critical problems including immune responses to grafted islets and side effects caused by overdosed immunosuppressive drugs. Herein, surface modification technology using poly(ethylene glycol) (PEG)-dendron was proposed to safeguard islets from the host immune system. PEG-dendron was synthesized by a divergent polymerization method and utilized to cover the islet antigen surface. Successful conjugation of PEG-dendron on the islet surface was achieved without affecting islet morphology, viability, and functionality at a concentration of 1.00%. Surface modification using PEG-dendron effectively prevented protein absorption and immune activation. Foremost, it improved the survival rate of islet grafts in vivo when combined with a low dose of immunosuppressive drugs. In conclusion, PEG-dendron is a potential candidate for the surface modification of pancreatic islets to mitigate immune responses after transplantation.

摘要

胰岛移植一直是治疗1型糖尿病的有效方法。移植的胰岛会根据血糖水平的变化释放胰岛素。然而,胰岛移植的临床应用受到了一些关键问题的阻碍,包括对移植胰岛的免疫反应以及过量免疫抑制药物引起的副作用。在此,提出了使用聚乙二醇(PEG)-树枝状大分子的表面修饰技术来保护胰岛免受宿主免疫系统的影响。PEG-树枝状大分子通过发散聚合法合成,并用于覆盖胰岛抗原表面。在浓度为1.00%时,成功地将PEG-树枝状大分子偶联到胰岛表面,且不影响胰岛的形态、活力和功能。使用PEG-树枝状大分子进行表面修饰可有效防止蛋白质吸附和免疫激活。最重要的是,当与低剂量免疫抑制药物联合使用时,它提高了胰岛移植在体内的存活率。总之,PEG-树枝状大分子是胰腺胰岛表面修饰以减轻移植后免疫反应的潜在候选物。

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