title: A fluorescent responsive hybrid nanogel for closed-loop control of glucose.
abstract: BACKGROUND
  The concept of closed-loop control of glucose, in which continuous glucose sensing is coupled to a fully automated insulin delivery device, without human input, has been an attractive idea for diabetes management. This study presents a new class of hybrid nanogels that can integrate glucose sensing and glucose-responsive insulin release into a single nano-object.
  
  
  METHODS
  Zinc oxide@poly[N-isopropylacrylamide (NIPAM)-acrylamide (AAm)- 2-aminomethyl-5-fluorophenylboronic acid (FPBA)] hybrid nanogels were synthesized and investigated for size, morphology, volume phase transition, photoluminescence properties, and in vitro insulin release under different glucose concentrations. Glucose sensing was performed both in phosphate-buffered saline (PBS) and in blood samples. The insulin release in PBS of varying glucose levels, as well as a stepwise treatment between two glucose levels (126.0 and 270.0 mg/dl), was performed to test the glucose-responsive insulin release ability of the hybrid nanogels.
  
  
  RESULTS
  Zinc oxide@poly(NIPAM-AAm-FPBA) hybrid nanogels can sensitively and selectively detect glucose in highly reproducible fluorescent signals over the clinically relevant glucose concentration range of 18-540 mg/dl. The glucose-responsive volume phase transition of the nanogels can further regulate the release of the preloaded insulin. The insulin release from the nanogels exhibits the slowest rate (~5% released in 76 h) at a normal glucose level (108.0 mg/dl) but becomes quicker and quicker as the glucose increases to higher and higher levels.
  
  
  CONCLUSIONS
  The rationally designed hybrid nanogel can optically signal the glucose level with high sensitivity and selectivity and simultaneously regulate the insulin release rate in response to the glucose reading, which shows a promising concept toward the development of a miniaturized closed-loop glycemic control system.
authors.affiliation: Department of Chemistry, College of Staten Island, Graduate Center, City University of New York, Staten Island, New York, USA. wuwtxmu@xmu.edu.cn
authors.forename: Weitai
authors.initials: W
authors.lastname: Wu
authors.forename: Shoumin
authors.initials: S
authors.lastname: Chen
authors.forename: Yumei
authors.initials: Y
authors.lastname: Hu
authors.forename: Shuiqin
authors.initials: S
authors.lastname: Zhou
mesh_terms: D000178:Acrylamides / Q000737:chemistry; D000180:Acrylic Resins / Q000737:chemistry / Q000493:pharmacokinetics; D000328:Adult; D015374:Biosensing Techniques / Q000295:instrumentation / Q000379:methods; D001786:Blood Glucose / Q000032:analysis*; D015190:Blood Glucose Self-Monitoring / Q000379:methods; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000628:therapy*; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D007328:Insulin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007332:Insulin Infusion Systems; D008954:Models, Biological; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000493:pharmacokinetics; D011094:Polyethyleneimine / Q000493:pharmacokinetics; D015034:Zinc Oxide / Q000737:chemistry
chemical_list: D000178:Acrylamides; D000180:Acrylic Resins; D001786:Blood Glucose; D005456:Fluorescent Dyes; D007004:Hypoglycemic Agents; D007328:Insulin; D000080385:Nanogels; C577850:poly(N-isopropylacrylamide-acrylamide-2-aminomethyl-5-fluorophenylboronic acid); C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; C067295:N-isopropylacrylamide; D015034:Zinc Oxide