title: Mesoporous silica nanoparticle-based double drug delivery system for glucose-responsive controlled release of insulin and cyclic AMP.
abstract: A boronic acid-functionalized mesoporous silica nanoparticle-based drug delivery system (BA-MSN) for glucose-responsive controlled release of both insulin and cyclic adenosine monophosphate (cAMP) was synthesized. Fluorescein isothiocyanate-labeled, gluconic acid-modified insulin (FITC-G-Ins) proteins were immobilized on the exterior surface of BA-MSN and also served as caps to encapsulate cAMP molecules inside the mesopores of BA-MSN. The release of both G-Ins and cAMP was triggered by the introduction of saccharides. The selectivity of FITC-G-Ins release toward a series of carbohydrate triggers was determined to be fructose > glucose > other saccharides. The unique feature of this double-release system is that the decrease of FITC-G-Ins release with cycles can be balanced by the release of cAMP from mesopores of MSN, which is regulated by the gatekeeper effect of FITC-G-Ins. In vitro controlled release of cAMP was studied at two pH conditions (pH 7.4 and 8.5). Furthermore, the cytotoxicity of cAMP-loaded G-Ins-MSN with four different cell lines was investigated by cell viability and proliferation studies. The cellular uptake properties of cAMP-loaded FITC-BA-MSN with and without G-Ins capping were investigated by flow cytometry and fluorescence confocal microscopy. We envision that this glucose-responsive MSN-based double-release system could lead to a new generation of self-regulated insulin-releasing devices.
authors.affiliation: Department of Chemistry, U.S. Department of Energy Ames Laboratory, Iowa State University, Ames, Iowa 50011-3111, USA.
authors.forename: Yannan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Brian G
authors.initials: BG
authors.lastname: Trewyn
authors.forename: Igor I
authors.initials: II
authors.lastname: Slowing
authors.forename: Victor S-Y
authors.initials: VS
authors.lastname: Lin
mesh_terms: D000818:Animals; D001897:Boronic Acids / Q000008:administration & dosage / Q000737:chemistry; D000242:Cyclic AMP / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005942:Gluconates / Q000737:chemistry; D005947:Glucose / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D001897:Boronic Acids; D003692:Delayed-Action Preparations; D005942:Gluconates; D007328:Insulin; D012822:Silicon Dioxide; D000242:Cyclic AMP; D005947:Glucose; C030691:gluconic acid