Development Of Controlled Drug Release System Based On The Interaction Between β-cyclodextrin And Small Molecules

Controlled-re lease drug delivery system is of great significance for diseasediagnosis and treatme nt, but the system is still exogenous for bio logical syste m. Owingto the comp lexity of biolo gical system, whether the drug has been released beforereaching the targets by various physio logy effects, whic h is vita l for drug treatmentsecurity. The n it has mome ntous meaning to realize targeted release drug deliverysystem and monitor the release of any type of drug mo lecule in real-time. The contentsof the thesis are as followed:1. Rationa l design of targets trigger drug release and fluorescence signa l outputsystem based on CD and aptamerIn this chapter， by comb ining the DNA triple-helix with hydrophobic hostmolecule β-Cyclodextrin (β-CD) to enhance the host-guest between β-CD andfluorescent dyes molecules(Tetraphenylporphyrin(TCPP), Rhodamine B(RhB)) for thefirst time, we constructed a target-mediate signal transduction system. In this system,we labeled β-CD on the3′-terminal of DNA, before addition of complementary DNAsequence, the host-guest interaction between β-CD and TCPP or RhB is re lative weak.However, upon addition of comp lementary DNA sequence to form trip le-helixstructure, the formed DNA triple-helix structure make two β-CD mo lecules close toeach other, which make β-CD molecules form more stable complexes with TCPP orRhB and cause the fluorescent intensity decrease of TCPP or RhB. Then, additio n oftargets which could destruct the trip le-helix structure, make β-CD mo lecules apartfrom each other and the host-guest interaction between β-CD and TCPP or RhBweakened, furthermore, the fluorescent inte nsity of TCPP or RhB increased.2. Redox-responsive controlled release system of mesoporous silicananopartic les(MSNs)Herein, we functionalized β-Cyclodextrin (β-CD) on the surface of MSNs anddesigned a volta ge responsive molecule gated release sys tem. In this syste m, beforeapplying a appropriate vo ltage, ferrocenedicarboxylic acid(Fc) strongly bound in thecavity of β-CD, which blocking the pores of MSNs, thus preventing the drug modelmo lecules cargo mo lecules p-coumaric acid(CA) fro m escaping fro m inside of theMSNs; Upon applying a appropriate voltage, Fc was oxid ized to positively chargedferrocenium species (Fc+). Owing to the weakening o f the bind ing affinity betweenβ-CD and Fc+, it can dissociate rapid ly fro m the cavity, which cause the op en of the pore and allow escape of the entrapped guest molecules.