Self-Regulated Glucose-Sensitive Neoglycoenzyme-Capped Mesoporous Silica Nanoparticles for Insulin Delivery

Abstract

"This is the peer reviewed version of the following article: Oroval, Mar, Paula Díez, Elena Aznar, Carmen Coll, María Dolores Marcos, Félix Sancenón, Reynaldo Villalonga, and Ramón Martínez-Máñez. 2016. Self-Regulated Glucose-Sensitive Neoglycoenzyme-Capped Mesoporous Silica Nanoparticles for Insulin Delivery. Chemistry - A European Journal 23 (6). Wiley: 1353 60. doi:10.1002/chem.201604104, which has been published in final form at https://doi.org/10.1002/chem.201604104. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving." ; [EN] We describe herein the preparation of glucose-sensitive capped mesoporous silica nanoparticles for insulin delivery. The new material consists of an expanded-pore nanometric silica support grafted with 1-propyl-1-H-benzimidazole groups, loaded with fluorescein isothiocyanate-labeled insulin (FITC-Ins) and capped by the formation of inclusion complexes between cyclodextrin-modified glucose oxidase (CD-GOx) and the benzimidazole groups grafted on the mesoporous support. Insulin delivery from the gated material in simulated blood plasma was assessed upon addition of glucose. Glucose is transformed by GOx into gluconic acid, which promoted the dethreading of the benzimidazole-CD-GOx inclusion complexes, allowing cargo release. Small quantities of this support would be needed to release the amount of insulin necessary to decrease diabetic blood glucose concentrations to regular levels. ; The authors thank the Spanish Government (projects CTQ2011-24355, MAT2015-64139-C4-1-R, CTQ2014-58989-P, and AGL2015-70235-C2-2-R (MINECO/FEDER)) and the Generalitat Valenciana (project PROMETEOII/2014/047) for support. M.O. thanks the Universitat Politecnica de Valencia for her FPI grant. P.D. thanks the Ministerio de Economia y Competitividad for her FPI grant (BES-2012-054066). C.C. thanks the Generalitat Valenciana for her postdoctoral contract VALi+D. ; Oroval, M.; Díez, P.; Aznar, E.; Coll Merino, MC.; Marcos Martínez, MD.; Sancenón ...