Synthesis Of Reduction-responsive Mesoporous Organsilica Nanoparticles As Anti-cancer Drug Carriers

Mesoporous organosilicas nanoparticles?MONs?are widely explored as drug carriers for its marked features,i.e.a.the biocompatibility and biodegradable skeleton to reduce the cell cytotoxicity;b.high surface area,large pore volume and suitable pore size?match some target molecules?to guarantee the drug loading efficiency;c.dodge most bio obstacles,but easily be trapped by tumor tissue due to the well-known enhanced penetration and retention?EPR?effects thus realize passive tumor accumulation.However,all these features could only afford high drug loading and delivery efficiency for MONs,their release efficiency is still far below expectation.It is widely accepted that controllable drug release is crucial for safe and effective cancer chemotherapy,because targeting release entrapped drugs could realize a minimum damage to normal cell,and a maximum utilization of drugs.Luckily,this objective could easily be realized through linking targeting ligand into the hybrid silicone matrix to afford them stimuli response capability.Moreover,some recently reports revealed that the nanocarrier aspect ratio is also crucial for cell capture and internalize.Bearing these theories in mind,we designed two redox response mesoporous organosilicas nanoparticles through incorporating S-S bond?a well-known redox response ligand?into their skeletons,the experimental details are described as below:In the second chapter we prepared binary mesopore dendritic mesoporous organosilica nanoparticles?HDMONs?through a growth-induced etching strategy by choosing dendritic silica as both hard template and inorganic silicon source while1,2-Bis?triethoxysilyl?ethane?BTEE?and Bis?3-?triethoxysilyl?propyl?-tetrasulfide?BTES?as dual organosilane source.The disulfide bond content could be controlled through simply regulation of the BTES feeding ratio.The high surface area,large pore volume and binary mesopore system?2 nm and 9 nm?in HDMONs made them suitable candidate for delivering anticancer drugs DOX?<2 nm?and BSA?14 nm×4nm×4 nm?.As we expect,HDMONs showed high fixation and encapsulation efficiencies for both DOX?234 mg/g and 93.6%?and BSA?221 mg/g and 44.2%?.In vitro drug release experiment revealed that most loaded drugs?96%within 30 h?would be released in redox environment?10 mM GSH solution,pH=5.6?due to the cracking of disulfide bond.Considering the EPR effects will facilitate localization in target tumor,while tumor cell will offer redox environment for stimuli-responsive release,HDMONs could be promissing passive targeting release carriers for chemotherapy.In the third chapter,mesoporous organosilica nanotubes were prepared through growth-induced etching method by using mSiO₂ spiral nanorods as both hard template and inorganic silicon source while BTEE and BTES as binary organosilica sources.The mSiO₂ nanorods were dissolved during assembly to residue a hollow structure,the successfully chiral transfer from the hard template to MONTs afford unique one-dimensional spiral characteristics,which highlight the effectiveness of this method.The nanotubes presented abundant mesopores to connect the inside and outside of their cavities,which means elevated loading amount compared with nanorods.Both the aspect ratio and disulfide bond content in MONTs could be adjusted by regulating the precursor ratio.The optimized MONTs presented high specific surface area?730 m²/g?and large pore volume?1.07 cm³/g?,which showed superior drug retention?244 mg/g?and encapsulation?97.6%?efficiencies for DOX.MONTs hold disulfide bond rich skeleton which afford them reduction response drug release ability.In simulated tumor reduction microenvironment?10 mM GSH,pH=5.6?,MONTs released 82%DOX,which is much higher than the amount in the simulated healthy organization microenvironment.In addition,MONTs is highly biocompatible,cytotoxicity test showed that most cells?94%?could survived in high concentration MONTs solution?100?g/ml?.Based on these achievements,we believe MONTs could serve as promising candidate for targeting delivery anti-cancer drug.