Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University , 4800 Caoan Road, Shanghai 201804, China.
Shanghai Tenth People's Hospital, Tongji University School of Medicine , Shanghai 200072, China.
J Am Chem Soc. 2017 Jun 7;139(22):7640-7647. doi: 10.1021/jacs.7b03219. Epub 2017 May 26.
Diabetes mellitus is a chronic, life-threatening illness that affects people of every age and ethnicity. It is a long-term pain for those who are affected and must regulate their blood glucose level by frequent subcutaneous injection of insulin every day. Herein, we propose a noninsulin and antidiabetic drug-free strategy for regulating blood glucose level by a nanosized "sugar sponge" which is a lectin-bound glycopolymersome capable of regulating glucose due to the dynamic recognition between the lectin and different carbohydrates. The glycopolymersome is self-assembled from poly(ethylene oxide)-block-poly[(7-(2-methacryloyloxyethoxy)-4-methylcoumarin)-stat-2-(diethylamino)ethyl methacrylate-stat-(α-d-glucopyranosyl)ethyl methacrylate] [PEO-b-P(CMA-stat-DEA-stat-GEMA)]. The lectin bound in the glycopolymersome has different affinity for the glucose in the blood and the glucosyl group in the glycopolymersome. Therefore, this sugar sponge functions as a glucose storage unit by dynamic sugar replacement: The lectin in the sugar sponge will bind and store the glucose from its surrounding solution when the glucose concentration is too high and will release the glucose when the glucose concentration is too low. In vitro, this sugar-breathing behavior is characterized by a remarkable size change of the sugar sponge due to the swelling/shrinkage at high/low glucose levels, which can be used for blood sugar monitoring. In vivo, this sugar sponge showed an excellent antidiabetic effect for type I diabetic mice within 2 days upon one dose, which is much longer than traditional long-acting insulin. Overall, this concept of "controlling sugar levels with sugar" opens new avenues for regulating the blood glucose level without the involvement of insulin or other antidiabetic drugs.
糖尿病是一种慢性、危及生命的疾病，影响着各个年龄段和种族的人群。对于受其影响的人来说，这是一种长期的痛苦，他们必须通过每天频繁地皮下注射胰岛素来调节血糖水平。在这里，我们提出了一种非胰岛素和无降糖药物的策略，通过纳米级的“糖海绵”来调节血糖水平，该“糖海绵”是一种结合了凝集素的糖基聚合物囊泡，由于凝集素与不同碳水化合物之间的动态识别，能够调节葡萄糖。该糖基聚合物囊泡由聚（环氧乙烷）-嵌段-聚[(7-(2-甲基丙烯酰氧乙氧基)-4-甲基香豆素）-嵌段-2-(二乙氨基)乙基甲基丙烯酸酯-嵌段-(α-D-吡喃葡萄糖基)乙基甲基丙烯酸酯] [PEO-b-P(CMA-stat-DEA-stat-GEMA)]自组装而成。结合在糖基聚合物囊泡中的凝集素有不同的亲和力，既能与血液中的葡萄糖结合，也能与糖基聚合物囊泡中的葡萄糖基结合。因此，这种糖海绵通过动态糖取代发挥葡萄糖储存单元的作用：当葡萄糖浓度过高时，糖海绵中的凝集素会结合并储存周围溶液中的葡萄糖；当葡萄糖浓度过低时，它会释放葡萄糖。体外，这种糖呼吸行为的特征是糖海绵由于在高/低糖水平下的膨胀/收缩而发生显著的尺寸变化，这可用于血糖监测。在体内，这种糖海绵在单次给药后 2 天内对 I 型糖尿病小鼠表现出优异的降血糖效果，这比传统的长效胰岛素长很多。总的来说，这种“用糖控制血糖”的概念为调节血糖水平开辟了新途径，无需涉及胰岛素或其他降糖药物。
