title: Alizarin Complexone Functionalized Mesoporous Silica Nanoparticles: A Smart System Integrating Glucose-Responsive Double-Drugs Release and Real-Time Monitoring Capabilities.
abstract: The outstanding progress of nanoparticles-based delivery systems capable of releasing hypoglycemic drugs in response to glucose has dramatically changed the outlook of diabetes management. However, the developed glucose-responsive systems have not offered real-time monitoring capabilities for accurate quantifying hypoglycemic drugs released. In this study, we present a multifunctional delivery system that integrates both delivery and monitoring issues using glucose-triggered competitive binding scheme on alizarin complexone (ALC) functionalized mesoporous silica nanoparticles (MSN). In this system, ALC is modified on the surface of MSN as the signal reporter. Gluconated insulin (G-Ins) is then introduced onto MSN-ALC via benzene-1,4-diboronic acid (BA) mediated esterification reaction, where G-Ins not only blocks drugs inside the mesopores but also works as a hypoglycemic drug. In the absence of glucose, the sandwich-type boronate ester structure formed by BA binding to the diols of ALC and G-Ins remains intact, resulting in an fluorescence emission peak at 570 nm and blockage of pores. Following a competitive binding, the presence of glucose cause the dissociation of boronate ester between ALC and BA, which lead to the pores opening and disappearance of fluorescence. As proof of concept, rosiglitazone maleate (RSM), an insulin-sensitizing agent, was doped into the MSN to form a multifunctional MSN (RSM@MSN-ALC-BA-Ins), integrating with double-drugs loading, glucose-responsive performance, and real-time monitoring capability. It has been demonstrated that the glucose-responsive release behaviors of insulin and RSM in buffer or in human serum can be quantified in real-time through evaluating the changes of fluorescence signal. We believe that this developed multifunctional system can shed light on the invention of a new generation of smart nanoformulations for optical diagnosis, individualized treatment, and noninvasive monitoring of diabetes management.
authors.affiliation: College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University , Changsha 410082, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zou
authors.affiliation: College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University , Changsha 410082, China.
authors.forename: Dinggeng
authors.initials: D
authors.lastname: He
authors.affiliation: College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University , Changsha 410082, China.
authors.forename: Linli
authors.initials: L
authors.lastname: Cai
authors.affiliation: College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University , Changsha 410082, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: He
authors.affiliation: College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University , Changsha 410082, China.
authors.forename: Kemin
authors.initials: K
authors.lastname: Wang
authors.affiliation: College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University , Changsha 410082, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University , Changsha 410082, China.
authors.forename: Liling
authors.initials: L
authors.lastname: Li
authors.affiliation: College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University , Changsha 410082, China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Li
authors.affiliation: College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University , Changsha 410082, China.
authors.forename: Xiaoya
authors.initials: X
authors.lastname: Su
mesh_terms: D000880:Anthraquinones / Q000737:chemistry; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy*; D016503:Drug Delivery Systems; D005453:Fluorescence; D005947:Glucose / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007328:Insulin / Q000097:blood; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D000077154:Rosiglitazone; D012822:Silicon Dioxide / Q000737:chemistry; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000880:Anthraquinones; D007328:Insulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C070804:alizarin complexone; D012822:Silicon Dioxide; D005947:Glucose
keywords: alizarin complexone; competitive binding; glucose-responsive; mesoporous silica nanoparticles; monitoring drug release