Biosensors and Nanotheranostics
Bionanotechnology, Drug Delivery, Therapeutics | online ISSN 3064-7789
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Volume 5 Number 1 2026
REVIEWS (Open Access)
Closed-Loop Nanotheranostic Systems: Biosensor-Triggered Insulin Release from Glucose-Responsive Nanogels
Sarah Stephenie John Sandanaraj 1*, Devyani Dogra 2, Chahat Antil 2
Biosensors and Nanotheranostics 5 (1) 1-8 https://doi.org/10.25163/biosensors.5110975
Submitted: 19 May 2026 Revised: 07 July 2026 Accepted: 15 July 2026 Published: 17 July 2026
Abstract
Insulin therapy has transformed diabetes from a fatal diagnosis into a manageable chronic condition, yet the way we deliver it has barely kept pace with how the disease actually behaves. Multiple daily injections and open-loop pump still ask patients to do, by hand and guesswork, what a healthy pancreas does continuously and without thought: match insulin output to a moving glucose target. The result is familiar—glycemic swings, injection fatigue, and the ever-present fear of hypoglycemia. This review examines an alternative that has matured rapidly over the past decade: closed-loop nanotheranostic systems in which glucose-responsive nanogels sense interstitial glucose and release insulin in proportion to it, with no human in the loop. We first dissect the three molecular recognition strategies that make such feedback possible—enzymatic oxidation by glucose oxidase, dynamic covalent binding by phenylboronic acid derivatives, and competitive displacement through lectins or glucose transporters—weighing each on kinetics, selectivity, and stability. We then trace how these chemistries are built into core–shell, dendrimer, and dual-crosslinked nanogel architectures, and how those materials are, in turn, embedded in microneedle patches and wearable biosensors to close the loop at the skin. Preclinical data are encouraging: single applications sustain normoglycemia for hours to days and resist glucose challenges without the rebound seen after bolus injection. What remains unresolved is translation—enzyme stability, boronate selectivity against competing diols, GMP-scale reproducibility, and the regulatory ambiguity of true drug–device combinations. The field, in short, has proven the concept and now faces the harder engineering.
Keywords: glucose-responsive nanogel; closed-loop insulin delivery; phenylboronic acid; glucose oxidase; microneedle patch; nanotheranostics; artificial pancreas
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