Study Of Catechol-Containing Compound Modified Mesoporous Silica Drug System

Mesoporous silica nanoparticles(MSNs)possess many excellent characteristics,such as good biocompatibility,rigidity,chemical stability,optical transparency,high specific surface areas,large pore volumes,uniform and tunable pore sizes,controllable surface functionalization,and resistance to microbial attack.In addition,MSNs effectively protect loaded cargo molecules against enzymatic degradation or denaturation induced by external environmental changes,because no swelling or porosity changes occur as a response to external stimuli,such as pH and temperature,etc.Furthermore,MSNs can be flexibly surface modified with a variety of organic functionalities,such as thiols,amines,carboxylic acids,alkoxy groups,and aromatic groups by the post-synthesis grafting or cocondensation(direct synthesis)sol-gel methods,resulting in highly useful organic-inorganic hybrid materials,which are considered to be promising nanocarriers and ideal scaffolds for targeted drug delivery such as ‘‘smart’’ cancer therapies.Inspired by the strong adhesive protiens secreted by mussels for attachment onto a wide range of substrates in wet condition,some reports indicated that polydopamine possesses the similar structure and strong adhesion to those of adhesive proteins.Polydopamine film can be formed on the surface of substrate in alkaline solution expeditiously,which results in the improvement of hydrophily and the chemical versatility of substrate due to the hydrophilic hydroxyl and amino groups of polydopamine.The polydopamine film can be used as an intermediate to anchor functional molecules on the surface through chemical bonds or other physical bonds.Polydopamine surface modifaction strategy is extremely useful because the process is simple and solvent-free.Moreover,due to the excellent cell adhesion and biocompatibility,polydopamine has been widely used in biomaterials.This article planned to incorporate dopamine derivatives and the stimuli-responsive switch with good biocompatibility onto the mesoporous silica,to obtain a different response of mesoporous silica drug delivery systems.The details about the studies were shown as follows:(1)Tannin as a gatekeeper of pH-responsive mesoporous silica nanoparticles for drug deliveryTannin has large steric hindrance and rich catechol groups,but related report on its use in the mesoporous silica drug delivery system were rare.In this section,we offered a pH-responsive drug delivery system based on mesoporous silica nanoparticles(MSNs)with tannin as a "gatekeeper".The pH-responsive Tannin-MSNs Tannin was synthesized by grafting Tannin on phenylboronic acid modified MSNs.In this system,loaded drug could be released in a low pH environment so as to achieve the goal of controllable release.The in vitro cellular cytotoxicity test to Marc-145 cells indicated that Tannin-MSNs were highly biocompatible and suitable to be used as drug carriers.Finally,the cellular uptake behavior of DOX@TanninMSNs in Hela cancer cell was investigated by confocal laser scan microscopy(CLSM).This method provides a new way for the preparation of mesoporous silica drug delivery system.(2)Enzyme-responsive,mussel mimetic coating for drug delivery based on MCM-41 mesoporous silicon nanoparticleEnzyme-responsive functional units with peptide bonds were widely used in biodegradable materials and liposome drug delivery system,while rarely reported in mesoporous silica drug delivery system.We obtained a unique enzyme-responsive MSNs drug delivery system by the polymerization reation of catechols with peptide bonds in alkaline solution.A dopamine derivative lysine-dopamine(LDA)was firstly synthesized,MCM-41-typed MSNs were then covered with polylysine-dopamine(PLDA)coating due to the self-polymerization of LDA in a Tris 8.5 buffer solution with rohdamine/DOX to form control-release drug delivery system(CDDS).In this system,DOX@PLDA-MSNs were pepsin-responsive and DOX release was controllable,for the peptide bonds in PLDA chains could be effectively cleaved by pepsin.The in vitro cellular cytotoxicity test demonstrated that LDA-MSNs were highly biocompatible and PLDAMSNs had certain inhibition effect on Hela cancer cells.Furthermore,CLSM results showed that DOX@PLDA-MSNs may be taken up by the cells through an edocytosis mechanism and the DOX were released in endocytic compartments.(3)Dual-sensitive,mussel mimetic coating for drug delivery based on MCM-41 mesoporous silicon nanoparticleAs we all known,the reported preparation of mesoporous silica drug delivery system would take at least three steps,including the modification by coupling agent,the grafting of responsive switch and the introduction of the "gatekeeper".However,the chemicals remained in mesoporous silica in each step could endanger human health.Therefore,the design of one-pot method for MSNs-based drug delivery has huge application potentials.In this chapter,one-pot strategy was used to prepare enzyme and redox doubleresponsive,mussel mimetic coating for MCM-41-typed MSNs drug delivery system.Cystine-dopamine(Cy-DA)was synthesized by amidation reaction and used as a monomer to self-polymerize to form polycystinedopamine(Poly-Cy-DA)coating on MCM-41-typed MSNs.Meanwhile,rohdamine/DOX was loaded to form Rh.B/DOX@Poly-Cy-DA-MSNs for drug delivery.The release experiments displayed that Rh.B/DOX@PolyCy-DA-MSNs had excellent redox and pepsin double-responsiveness due to the special structure of Poly-Cy-DA.The in vitro cellular cytotoxicity test demonstrated that Poly-Cy-DA-MSNs had high biocompatibility and outstanding inhibition on Hela cells and CLSM proved the drug controllability.The above results showed that Poly-Cy-DA-MSNs are promising platforms to construct double-responsive controlled drug delivery systems for stomach and cancer therapy.(4)Poly-cystine-dopamine dual-sensitive,mussel mimetic coating for drug delivery based on SBA-15 mesoporous silicon nanoparticlePolydopamine could adhere to various surfaces,which make it widely applied in surface modification fields.To prove that the synthetic Poly-CyDA had the similar properties,it was introduced to drug delivery system based on SBA15-MSNs and the mussel mimetic coating was coverd on glass slides.TEM-EDS,TGA,XRD and BET demonstrated that SBA15-MSNs were uniformly coated by Poly-Cy-DA and rhodamine was effectively loaded on Poly-Cy-DA-MSNs.In vitro release tests showed that the Rh.B(rhodamine)/DOX@Poly-Cy-DA-MSNs were redox-responsive and pepsin-responsive due to that the disulfide bonds and the peptide bonds in Poly-Cy-DA chains can be effectively cleaved by GSH(glutathione)and pepsin respectively,which resulted in the degradation of Poly-Cy-DA and then the drug release.In addition,the simulation experiments on glass slides visually verified the double-responsiveness of Poly-Cy-DA coating and water contact angle data showed Poly-Cy-DA played the role of surface modification.All the results concluded that Poly-Cy-DA can be used to the preparation of both double-responsive drug release system and dualresponsive mussel-mimetic coating in the field of surface modification.