Glucose Responsive Insulin in aptamer targeted nanoparticles

Insulin-dependent diabetes mellitus (IDDM) therapy is based on supplying insulin externally when blood glucose levels were determined out of the normal range, and it is vital for diabetic patients. The blood glucose measurement is mostly performed by finger prick before each insulin injection, which often reduces patients’ quality of life and can occasionally lead to life-threatening complications. Although patch-based glucose detection is becoming more common, it remains costly. Similarly, automatic insulin delivery devices that provide insulin to patients’ blood in response to circulating glucose levels exist but are not yet widely accessible. Thus, artificial nanopancreas concept can combine glucose detection and automated release of insulin directly into blood stream. The major challenge in the realization of an artificial pancreas through nanoparticles is the lack of a gating mechanism which can directly be adjusted to close or open in respond to blood glucose. This study aims to develop a glucose-responsive insulin provider in the form of nanoparticles with a self-controlled aptamer-based release mechanism. In this study, 6-week-old female Sprague Dawley rats were used, and diabetes was induced by the administration of streptozotocin (STZ) (60 mg/ kg b.w) intraperitoneally. The glucose responsive aptamer sequence selected by SELEX methodology and dissociation constant (KD) was determined. The aptamer gated mesoporous silica nanoparticles were loaded with insulin and capped by the aptamer gates. The conjugates were characterized by DLS, FRTIR and SEM analysis. The diabetes induced rats having glucose level over 300 mg/dl were divided into three groups: no treatment, glucose responsive aptamer gated mesoporous silica nanoparticles loaded with insulin injected group and only mesoporous silica nanoparticles loaded with insulin injected group (n=4). After the injection, the blood glucose levels followed up to 4 hours. Selected glucose aptamer showed the highest binding affinity, with KD value of 927 ± 37 µM. The treatment group maintained the blood glucose level below 150 mg/dl more than 4 hours while control groups had blood glucose levels more than 300 mg/dl. In conclusion, the glucose-responsive, aptamer-gated mesoporous silica nanoparticles developed in this study effectively reduced and maintained blood glucose levels in diabetic rats, demonstrating their potential as a promising alternative to traditional insulin delivery methods for more precise, self-regulated diabetes management. Health Institute of Turkiye, Project no: 16807 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.