Construction And Analytical Application Of Multifunctional Silica Dioxide-based Drug Nanocarrier

Tumors are a global public threat to human health.Exploring SiO₂ based multifunctional drug nanocarrier for precise tumor theragnostic is still facing tremendous challenge in analytical sensing and nanomedicine interdisciplinary area.This paper aims at the complicated construction process of current smart response drug carrier,multi-therapeutic collaboration and inefficient integration in the field of drug delivery and sensing.Try to simplify the synthesis of nanocontainers,optimize multi-therapeutic synergy strategies and develop a novel molecular sensing mediated theragnostics.By using nano SiO₂as a carrier,the targeted nano carriers which respond to glutathione(GSH)and p H/GSH are constructed after surface functional regulation.At the same time,based on the optical absorption,oxidation characteristics and the Fenton activity of manganese dioxide(MnO₂)nanomaterials.The therapeutic reagents delivery is realized with the GSH sensing procedure,and finally develop a new theragnostics method.The research works are as follows:Section 1:Bovine serum albumin modified mesoporous silica nanoparticle for redox rsponsive target drug release.The reduction response nano carrier is constructed by using bovine serum albumin as response functional group and nano valve at the same time due to its endogenous disulfide bond and higher molecular weight.In this section,a novel GSH responsive nanocarrier is designed by assembling the folate modified bovine serum albumin onto the surface amido grafted mesoporous silica nanoparticle via amide bonding for epirubicin delivery.Further,the GSH triggered drug release,folate receptor-mediated tumor cell recognition and cell growth inhibition are discussed.It is demonstrated that the strategy of integrating GSH responsive functional groups and nanovalves on the same natural polymer is feasible to optimize the construction of novel GSH responsive targeting nanocarriers.Section 2:Tumor microenvironment responsive mesoporous silica nanoparticle for dual delivery doxorubicin and chemodynamic reagents.The combination of chemotherapy and chemodynamic therapy provides an important way to enhance the inhibition of tumor cells and therapeutic effect.However,Mn based Fenton reagent still faces the challenge of weak reactivity and the limited reactive oxygen species generation.Therefore,mesoporous silica nanoparticle is orderly assembled the Fe³⁺-polydopamine and folate modified mineralized MnO₂ bovine serum albumin to innovatively integrate the two Fenton reagents.By investigating the Fenton effect,drug release and tumor cell recognition performance of the carrier,the results show that the double Fenton reagent assembly significantly ameliorating the ability of reactive oxygen species generation and enhance the inhibition of tumor cell growth,which provided new strategy for the development of a combined therapy platform.Section 3:Biodegradable SiO₂@MnO₂ nanocomposite for glutathione sensing and tumor cell theragnostics.The combination of analytical sensing strategy and drug delivery provides an attractive programme for the development of novel theragnostics system.In this section,a new core shell nanoprobe for human serum GSH determination and photodynamic and chemodynamic synergistic therapy is designed by using dye doped SiO₂(FS)as the core,methylene blue loaded porous MnO₂ as the shell,and the polyethylene glycol for shielding the MB from premature leaking.Where FS is the energy donor,MnO₂ is used as both energy receptor,Fenton reagent and photosensitizer methylene blue loading container.Based on fluorescence resonance energy transfer,a sensing method for GSH is established.In addition,FSMP generates Mn²⁺while releasing photosensitizer in the sensing process.Under the laser irradiation and tumor environment overexpressed H₂O₂,the photodynamic and chemodynamic synergy is realized,which illustrates that FSMP has a wide application in sensing strategy guided theragnostics area.Section 4:DMSN@MnO₂ nanocarrier for dual glutathione sensing and targeted tumor cell detectionIn this section,a new nanocarrier is designed by in situ redox reaction between the KMnO₄ and amino grafted dendritic mesoporous silica nanoparticle,further modifying the active target molecular folic acid via amidation process for camptothecin loading(denoted as CPT/DM-FA).Based on the fluorescence characteristics of CPT and the absorption capacity of MnO₂,a GSH fluorescence sensing method is established.Meanwhile,the oxidation color change between MnO₂ and 3,3',5,5'-tetramethylbenzidine(TMB)is used to construct absorbance monitor method to GSH.Based on the principle of absorbance sensing method and total GSH concentration in series number of tumor cells,CPT/DM-FA could specifically count tumor cells.We believe this CPT/DM-FA has a significant advantage in the development of multifunctional nano platform.