Controllable Synthesis Of Hollow Mesoporous Organic Silicon And Their Application In Cancer Diagnosis And Therapy

Mesoporous Silica Nanoparticles(MSNs)show great potential in cancer diagnosis and therapy due to their high stability and unique functionalities.However,the frameworks of MSNs are composed of hard-broken O-Si-O bonds,and their biodegradability and biocompatibility are still under debate.Herenin,a kind of organic-inorganic hybridized hollow mesoporous nanoparticles(HMONs)have been successfully synthesized based on a “chemical homology” mechanism.The disulfide bonds(S-S)were directly incorporated into the silica framework,which greatly improved the biodegradability of inorganic nanoparticles.In this thesis,we studied the controllable synthesis of HMONs,their biodegradability and applications in drug delivery and magnetic resonance imaging-guided sonodynamic cancer therapy.The detailed contents include the following three prats.(1)Molecularly organic-inorganic hybridized hollow mesoporous organosilica nanocapsules(HMONs)with high dispersity and sub-50 nm particle size have been synthesized based on a “chemical homology” mechanism.Here,a physiologically active disulfide bond(-S-S-)was directly incorporated into the silica framework.The particle size and mesopores of HOMNs could be tuned by changing the initial volume ration of organosilica precursors.The results showed that when the adopted volume ratios of TEOS and BTDS were increased from 5/6 to 5/12,the mesopore size could be effectively enlarged while the particle diameter was reduced accordingly.The degradation test in simulated body fluid and 4T1 cancer cells demonstrated that HMONs could degrade in the reducing environment,which was attributed to the disulfide bonds in the frameworks of HMONs that can break up under reducing condition.(2)Design of HMONs as nanocarriers for drug delivery.HMONs own large cavities,which provide enough room for drug loading.Using DOX as a model drug,HMONs had a high DOX-loading capacity(566 mg/g)and loading efficiency(94.3%).In vivo results showed that the physiologically active disulfide bonds can break up when contacting the reducing microenvironment of tumor tissue,and thereby improved the releasing amount of drug as well as accelerated the biodegradation of drug carries.Therefore,HMONs-based durg delivery system could induce high chemotherapeutic efficacy in tumors and more less harm to the body.(3)Design of metalloporphyin anchored HMONs for efficient MRI-guided sonodynamic therapy(SDT).HMONs own abundant silanol groups on the surfaces of mesopores and the cavity,and are easy to be modified with other functional groups.In this work,manganese protoporphyrin(MnPpIX)was proposed to graft into HMONs.Protoporphyrin as a sonosensitizer can be used for SDT,manganese in prophyrin rings can be used as T1 contrast agent for magnetic resonance imaging(MRI),which can be used for highly efficient MRI-guided sonodynamic cancer therapy.The reaults showed that the MnPpIX-modified HMONs have good biosafty,biocompatibility and remarkable sonodynamic cancer therapeutic effect with a high tumor-inhibition rate of 75.4%.In summary,we have successfully developed a simple but versatile “chemical homology” strategy to synthesize organic-inorganic hybrid HMONs with sub-50 nm particle size.Especially,physiologically active disulfide bond(-S-S-)was directly incorporated into silica framework to endow the carriers with tumor-specific biodegradability.The biodegradation process and corresponding chemical mechanism were systematically evaluated.The unique tumor-specific biodegradation of HMONs can bring with tumor-responsive anticancer drug releasing by the biodegradation-induced disintegration of the framework.In addition,the well-defined mesoporous structure facilitates the high loading of sonosensitizers(PpIX)and the subsequent chelating of paramagnetic transitional metal Mn ions based on metalloporphyin chemistry,endowing the composite sonosensitizers with excellent MR imaging performance for SDT guidance and monitoring.This research work provides a paradigm that the organic-inorganic hybridized framework can endow the nanocarrier with unique biological effects suitable for biomedical application,which may benefit the development of drug delivery systems with unique functionality and performance in cancer therapy...