| Target-responsive controlled release systems are very important in enhancingdrug therapeutic effect, reducing drug side effect and toxicity to normal cells. Chosingof supportor and cap agent is significant in designing target-responsive controlledrelease system. MCM-41-type mesoporous silica nanoparticle is a good candidate fordrug carrier because of its parallel pores with two openings which make it easy to loadand release drug. As one kind of DNA with special stucture, aptamer is the bestcandidate in designing target-responsive controlled release system because it canspecificly combine with its target with strong affinity. Herein, we chose MSN as drugcarrier, aptamer as target recognition molecule, which paired with diffirent parts ofcomplementary DNA to form different spatial structure DNA to cap the pores of MSN,designed two ATP-responsive controlled release system. Mainly including these twoparts:1. Aptamer-Containing Sandwich-Type DNA Capped Mesoporous SilicaNanoparticles for ATP-Responsive Controlled ReleaseHere, making use of the specific binding property of ATP-aptamer with ATP, anoriginal and facile ATP-responsive controlled release system consisting ofmesoporous silica nanoparticles (MSN) capped with aptamer-containingsandwich-type DNA has been designed. In this system, ATP aptamer was firsthybridized with arm single-stranded DNA1(arm ssDNA1) and arm single-strandedDNA2(arm ssDNA2) which were modified with alkyn group in their5’ end to formthe sandwich-type DNA structure and then grafted onto the nitrine functionalizedMSN surface through click chemistry approach, resulting in blockage of pores andinhibition of guest molecules release. As a proof-of-principle, Ru(bipy)32+wasselected as the guest molecules, and the ATP-responsive release of Ru(bipy)32+havebeen investigated. The results demonstrate that the dye released percentage can reach83%after treatment with20mM ATP for7h. Moreover, the ATP-responsive behaviorshows high selectivity with ATP analogues. However the leakage of Ru(bipy)32+molecule is neglectable if ATP was not added, indicating an excellent cappingefficiency. Interestingly, this system can respond not only to the commercial ATP butalso to the ATP extracted from living cells. This proof of concept might promote theapplication of ATP-responsive devices and can also provide an idea to design various target-responsive systems using other aptamers as cap.2. Aptamer-Containing Triple Helix DNA Capped Mesoporous SilicaNanoparticles for ATP-Responsive Controlled ReleaseThree strand DNA is formed by three nucleotide chains through hydrogen binding.Generally, the third chain insert into the major groove of W-C double helix, twinstedparallel or antiparallel to form three-helix DNA, named triple helix DNA. On thebasis of the previous work, a novel aptamer containing triple helix DNA cappedATP-responsive mesoporous silica nanoparticle (MSN)-based controlled releasesystem has been designed. In this system, the ATP-aptamer was extended for7basesin its3’ end and5’ end, and then hybridized with single stranded DNA (ssDNA) whichmodified with alkyn group in its5’ end to form the triple helix DNA structure andthen grafted onto the MSN surface through click chemistry approach, resulting inblockage of pores and inhibition of guest molecules release. As a proof-of-principle,Ru(bipy)32+was selected as a model guest molecule, and the control release ofRu(bipy)32+had been investigated. The results demonstrated that the system had goodcapping efficiency and excellent ATP response behavior. The leakage of Ru(bipy)32+molecule was neglectable in the absence of ATP and the dye released percentage canreach90%after treatment with10mM ATP for7h. This system was proved to bemore effective than the last one. We believe that the triple helix DNA cappedATP-responsive MSN system could extend the practical application of aptamer inbio-analysis detection area and controlled release area. |
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