Mesoporous Silica Composite Nano-carriers Based On Self-polymerization Of Polyphenols

Mesoporous silica nanomaterials(MSNs)have the advantages of high specific surface area and pore volume,adjustable mesopore pore size,good biocompatibility,and have been developed into new drug delivery carriers.Although the specific chemical modification of the material can achieve effective packaging of drugs and response to the stimulus signal,it is still urgent to solve the problems as follows for the biological application of mesoporous silica system:(1)low drug loading;(2)restricted functionalization of the particle surfaces.Thus,key issues for the research and development of such drug carrier materials include:(1)increasing the affinity of mesoporous silica nanoparticles and anticancer drugs(especially hydrophilic anticancer drugs);(2)achieving higher drug loading degree and easy controlled drug release by means of material integration or embedding.Polyphenols have excellent bioadhesive and cohesive properties due to their catechol or pyrogallol groups.They are used as biomimetic materials that have a good application prospects in the fields of surface coating,composite nanoparticle preparation,drug delivery,and other fields.Mesoporous silica nanoparticles and polyphenols are attractive representatives of inorganic materials and organic materials,respectively.Possessing great application prospects in fields of drug delivery and controlled release.Based on the study of polyphenols,this research combined their excellent properties with the characteristics of mesoporous silica nanomaterials,to prepare ideal composites for drug loading and release.The main contents are as follows:(1)Polydopamine coatings in confined nanopore space: toward improved retention and release of hydrophilic cargoAmino-modified mesoporous silica nanoparticles(MSN-NH2)were synthesized through cetyltrimethylammonium bromide(CTAB)as template,tetraethyl orthosilicate and triaminopropyltriethoxysilane as silicon source.MSN@PDA nanocomposite particles preparation though construction of polydopamine coating on MSN surfaces mediated by oxidant induced surface polymerization.Transmission electron microscopy(TEM),FTIR,Dynamic light scattering(DLS)and BET were showed that: particles are coated with a thin layer of polydopamine with an average diameter of ~70 nm.As a carrier,MSN@PDA particles were loaded with anti-cancer drug doxorubicin(DOX).Due to the π-π stacking effect between polydopamine and aromatic anthracycline skeleton,MSN@PDA particles have high drug loading degree and sustained release ability.The rich catechol groups in the coating renders the composite nanoparticles with the ability to chelate the metal ions.Therefore,the pH-responsive "catechol-metal-drug" coordination system was established for pH response drug release systems.Cytotoxicity and confocal laser confocal microscopy analysis showed that MSN@PDA particles had good cytocompatibility and could release DOX into tumor cells.(2)Silica-assisted incorporation of polydopamine into the framework of porous nanocarriers by a facile one-pot synthesisInspired by bio-silicification,the effects of polydopamine on the morphology and structure of MSN particles were investigated with the polymerization of dopamine and the hydrolysis condensation of the silicon source at the nanoscale,by controlling the molar ratio of dopamine to silicon source(tetrahexyl orthosilicate,TEOS).Silica-assisted incorporation of polydopamine into the framework of porous nanocarriers by a facile one-pot synthesis.The spherical PDA-MSN composite particles with a high specific surface area(960 m2/g)and a peak pore size of 4 nm.The PDA-MSN particles were characterized by transmission electron microscopy(TEM),BET,Raman and so on.High dopamine ratios resulted in phase separation of poly dopamine and self-nucleation of polymer nanoparticles.Silicic acid interacts with polydopamine through the catechol groups in poly-dopamine,which in turn delays the condensation of the silica and promotes the polymerization of the dopamine.The polydopamine was successfully incorporated into the porous silicon network.PDA-MSN particles show great potential in drug delivery systems.In terms of high drug loading capacity(1000 μg/g),sustained drug release and efficient delivery of DOX to HepG2 cells.(3)Oxidized induced tannic acid surface deposition: Acid responsive drug delivery systemIn the fourth chapter,the interaction between the surface of MSN particles and tannic acid(TA)was first studied.The efficient surface deposition of tannic acid and the distribution was explored by thermogravimetric analysis(TGA),HPLC,and nitrogen sorption measurements.Metal-polyphenol networks(MPN)and boratepolyphenol networks(BPN)as responsive drug release switches were constructed in situ on drug loaded MSN by separating the TA deposition and the crosslinking between tannic acid and Zn2+,benzene-1,4-diboronic acid(BDBA)into two steps under aqueous conditions,leading to the synthesized MSN@TA-Zn and MSN@TA-BDBA composite particles.By using DOX as a mode drug,MSN@TA-Zn and MSN@TA-BDBA particles can achieve high loading degree and pH response release.MSN@TA-Zn particles have higher pH sensitivity.In vitro cytotoxicity experiments showed that MSN@TA-Zn and MSN@TA-BDBA particles had good biocompatibility and could kill tumor cells effectively.They can be used as a drug carrier for cancer treatment.