Sugar-Breathing Glycopolymersomes for Regulating Glucose Level

J Am Chem Soc. 2017 Jun 7;139(22):7640-7647. doi: 10.1021/jacs.7b03219. Epub 2017 May 26.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose*
  • Diabetes Mellitus, Experimental
  • Humans
  • Lectins / chemistry*
  • Liver / chemistry
  • Liver / cytology
  • Methacrylates / chemistry*
  • Microscopy, Electron, Transmission
  • Models, Molecular

Substances

  • Blood Glucose
  • Lectins
  • Methacrylates
  • diethylaminoethyl methacrylate