title: Controlled release of silyl ether camptothecin from thiol-ene click chemistry-functionalized mesoporous silica nanoparticles.
abstract: As efficient drug carriers, stimuli-responsive mesoporous silica nanoparticles are at the forefront of research on drug delivery systems. An acid-responsive system based on silyl ether has been applied to deliver a hybrid prodrug. Thiol-ene click chemistry has been successfully utilized for tethering this prodrug to mesoporous silica nanoparticles. Here, by altering the steric bulk of the substituent on the silicon atom, the release rate of a model drug, camptothecin, was controlled. The synthesized drug delivery system was investigated by analytical methods to confirm the functionalization and conjugation of the mesoporous silica nanoparticles. Herein, trimethyl silyl ether and triethyl silyl ether were selected to regulate the release rate. Under normal plasma conditions (pH 7.4), both types of camptothecin-loaded mesoporous silica nanoparticles (i.e., MSN-Me-CPT and MSN-Et-CPT) did not release the model drug. However, under in vitro acidic conditions (pH 4.0), based on a comparison of the release rates, camptothecin was released from MSN-Me-CPT more rapidly than from MSN-Et-CPT. To determine the biocompatibility of the modified mesoporous silica nanoparticles and the in vivo camptothecin uptake behavior, MTT assays with cancer cells and confocal microscopy observations were conducted, with positive results. These functionalized nanoparticles could be useful in clinical treatments requiring controlled drug release.
  
  
  
  As the release rate of drug from drug-carrier plays important role in therapy effects, trimethyl silyl ether (TMS) and triethyl silyl ether (TES) were selected as acid-sensitive silanes to control the release rates of model drugs conjugated from MSNs by thiol-ene click chemistry. The kinetic profiles of TMS and TES materials have been studied. At pH 4.0, the release of camptothecin from MSN-Et-CPT occurred after 2h, whereas MSN-Me-CPT showed immediate drug release. The results showed that silyl ether could be used to control release rates of drugs from MSNs under acid environment, which could be useful in clinical treatments requiring controlled drug release.
authors.affiliation: Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China. Electronic address: jiefu@zju.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Fu
authors.affiliation: Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China.
authors.forename: Tianfu
authors.initials: T
authors.lastname: Wang
authors.affiliation: Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China.
authors.forename: Xiuyang
authors.initials: X
authors.lastname: Lu
mesh_terms: D002166:Camptothecin / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002470:Cell Survival / Q000187:drug effects; D057930:Click Chemistry / Q000379:methods*; D004337:Drug Carriers / Q000737:chemistry; D004986:Ether / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D056951:Photoelectron Spectroscopy; D016062:Porosity; D012821:Silanes / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013818:Thermogravimetry; D059008:Time-Lapse Imaging
chemical_list: D004337:Drug Carriers; D012821:Silanes; D013438:Sulfhydryl Compounds; D004986:Ether; D012822:Silicon Dioxide; D002166:Camptothecin
keywords: Click chemistry; Drug delivery; Mesoporous silica nanoparticles; Silyl ether