Studies On Stimuli-responsive Controlled Release And Analytical Detection Using Reversible And Reproducible Mesoporous Silica

Mesoporous silica nanoparticles, due to its high surface area, large mesoporousvolume, uniform tunable size （2-30nm）, ordered mesoporous structure （multiplearrangement）, the unique mesoscopic structure and physical and chemical properties,show a broad application in catalysis, adsorption, macromolecules transformation,protein isolation, optical electromagnetic materials, especially in stimuli-responsivecontrolled release and biosensors. But recent controlled release systems have somedisadvantages such as lack of reversibility and reproducibility. Consequently, thispaper will employ mesoporous silica nanoparticles as the nanocarriers to design thereversible stimuli-responsive release system and develop reproducible methods formercury detection and removal. The main research aspects are as follow:1. A light-responsive reversible controlled release system using thymine-modifiedmesoporous silica nanoparticlesIn this paper, a reversible light-responsive controlled release system based onmesoporous silica nanoparticles （MSN） functionalized with thymine derivatives isdesigned and demonstrated. The closing/opening protocol and release of the entrappedguest molecules is related by a photodimerization-cleavage cycle of thymine upondifferent irradiation. In the system, thymine derivatives with hydrophilicity andbiocompatibility were grafted on the pore outlets of MSN. The irradiation with365nm wavelength of UV light to thymine-functionalized MSN leaded to the formation ofcyclobutane dimer in the pore outlet, subsequently resulted in blockage of pores andstrongly inhibited the diffusion of guest molecules from pores. With240nmwavelength of UV light irradiation, the photocleavage of cyclobutane dimer openedthe pore and allowed release of the entrapped guest molecules. As aproof-of-the-concept, Ru（bipy）32+was selected as the guest molecule. Then thelight-responsive loading and release of Ru（bipy）32+have been investigated. Theresults indicated that the system had excellent loading amount （53μmol g-1MSN） andcontrolled release behavior （82%release after irradiation for24h）, and thelight-responsive loading and release procedure exhibited a good reversibility. Besides,the light-responsive system loaded with Ru（bipy）32+molecule could also be used as alight-switchable oxygen sensor.2. A photoresponsive reversible controlled release system using i-motif DNA andMGCB functionalized mesoporous silica nanoparticles This paper proposed a novel photoresponsive reversible controlled release systemusing mesoporous silica nanoparticles functionalized with i-motif DNA and malachitegreen carbinol base （MGCB）. In this system, MGCB was immobilized on thenanochannel walls of MSN as a light-induced hydroxide ion emitter, and i-motif DNAwas grafted on the surface of MSN as a cap. The photoirradiation with365nmwavelength of UV light made MGCB dissociate into malachite green （MG） cation andOH–ion, which induced i-motif DNA to unfold into the single-stranded form. Thus,the pores were uncapped and the entrapped guest molecules were released. After thelight was turned off, the MG cation recombined with the OH–ion. The single-strandedDNA switched back to i-motif structure to cap the pore again. Rooting form MGCBmediated DNA conforma-tion changes, the quadruplex DNA-gated switch could beeasily operated by turning the light on or off. Importantly, the opening/closingprotocol was highly reversible and a partial cargo release could be easily achieved atwill. This proof of concept might promote the application of DNA in the controlledrelease and could also provide an idea to design various photon-fueledcontrolled-release systems by using a combination of photoirradiated pH-jump systemand other kinds of pH-sensitive linkers.3. A reversible intracellular acid-responsive controlled release system using T-Hg2+-Tbase pairs mediated double-stranded DNA-capped mesoporous silica nanoparticlesThis paper proposed a reversible intracellular pH-responsive controlled releasesystem consisting of mesoporous silica nanoparticles （MSN） functionalized on thepore outlets with T-Hg2+-T base pairs mediated double-stranded DNA （dsDNA1）. Inthis system, the dsDNA was grafted on the MSN surface as a nanoscopic cap. Thecontrolled release system was closed at neutral pH but opened at pH5.0due to thedissociation of T-Hg2+-T structures and the subsequent melting of dsDNA1. As aproof-of-the-concept, the doxorubicin （Dox） was loaded into the dsDNA1-modifiedMSN （MSN-dsDNA1） as a model drug. Release-profile studies in water showed thatno Dox leaked when the cap was closed and that release occurred immediately afteracidification. By alternately changing the pH from5.0to7.2, the DNA cap could beswitched “on” and “off” and thereby regulated the partial release of Dox. Further invitro studies demonstrated that the Dox-loaded MSN-dsDNA1（MSN-Dox-dsDNA1）could be endocytosed and accumulated within endosomes and lysosomes, followed byserving as a delivery for the controlled release of Dox into the cell nuclei at theendosomal and lysosomal pH level inside live HeLa cells. The cell viability resultsshowed that the inhibitory concentration （IC50） of MSN-Dox-dsDNA1was low （≈ 12.5μg mL–1）, while MSN-dsDNA1（IC50>100μg mL–1） had a negligiblecytotoxicity at the same concentration, indicating that MSN-dsDNA1was fairlybiocompatible and indeed served as a drug-carrier for intracellular controlled release.We believe that the nanosystem may prove to be a significant step toward thedevelopment of an intracellular acid-responsive drug delivery system that is apromising candidate in vivo delivery of therapeutic agents.4. Reversible bioresponsive controlled release system using mesoporous silicananoparticles capped with C-Ag+-C base pairs mediated double-stranded DNAWe reported a novel reversible bioresponsive controlled-release system consistingof mesoporous silica nanoparticles （MSN） functionalized with C-Ag+-C base pairsmediated double-stranded DNA. In this system, a unique sequential cytosine （C）-richDNA as the smart molecule-gated switch was grafted on the mesoporous silicananoparticles （MSN） surface. In the presence of Ag+ions, the closer C-rich DNAcould hybridize each other by the formation of C-Ag+-C structure based onmetal-dependent pairs of two nucleobases, resulting in blockage of pores and packageof guest molecules. By a competitive displacement reaction, the duplex DNA withC-Ag+-C structure deformed into single-stranded DNA in the presence ofthiol-containing molecule, such as dithiothreitol （DTT）, which gave rise to uncappingand the subsequent release of the entrapped guest molecules. The reversible open andclosed states of DNA molecule-gated switch could be easily achieved by alternatingaddition of Ag+-linkers and DTT molecules. Our results demonstrated that the systemhad excellent loading amount （43μmol g–1） and good controlled release behavior.Moreover, the system could enter the cells through endocytosis and showed a lowcytotoxicity even with treatment in a high concentration （200μg mL–1）. We believedthat the stimuli-responsive controlled MSN release system based on the smartmolecule-gated switch could play an important role in the development intracellulardelivery nanodevices.5. Regenerable multifunctional mesoporous silica nanocomposites for simultaneousdetection and removal of mercury （II）Mercury (Hg²⁺) is a highly toxic and widespread environmental pollutant. Herein, aregenerable core-shell structured magnetic mesoporous silica nanocomposite withfunctionalization of thymine （T） and T-rich DNA （denoted as Fe3O4@nSiO2@mSiO2-DNA-thymine） has been developed for simultaneous detection and removal ofHg²⁺. The detection mechanism is based on Hg²⁺-mediated hairpin structure formedby T-rich DNA functionalized on the surface of the nanocomposite, where, upon addition of SYBR Green I dye, strong fluorescence is observed. In the absence ofHg²⁺, however, addition of the dye results in low fluorescence. The limit of detectionfor Hg²⁺in a buffer is2nM by fluorescence spectroscopy. Simultaneously, thenanocomposites-based sensors feature a selective binding with Hg²⁺between twothymines immobilized at the interior surface of the mesopores and exhibits efficientand convenient Hg²⁺removal by a magnet. Kinetic study reveals that the Hg²⁺removal is a rapid process. The applicability of the developed materials isdemonstrated to detect and remove Hg²⁺from samples of Xiangjiang river waterspiked with Hg²⁺. In addition, distinguishing aspects of the nanocomposite for Hg²⁺detection and removal also include the regeneration using a simple acid treatment andresistance to nuclease digestion. Similar process can be used to functionalizeFe3O4@nSiO2@mSiO2nanocomposite with other nucleic acids and small moleculesfor environmental and biomedical applications.