Multifunctional Mesoporous Organosilica For Drug Delivery And Bioimaging

Recently,the nanocarriers mediated drug delivery systems have attracted much attention in the field of biomedical application for reducing the adverse effects and improving cancer therapy efficacy of anticancer drugs.Among the materials for drug delivery,mesoporous silica nanoparticles provide a valuable platform for the construction of various multifunctional intelligent delivery systems due to their distinct features,e.g.,large surface area and pore volume,facile functionalization and favorable biocompatibility.In the present thesis,the mesoporous organosilica nanoparticles(MONs)in combination with organic molecules and functional polymers are fabricated by feasible methods.These multifunctional nanocarriers could be used for controlling drug release,tracking the behavior of nanocarriers and enhancing the cancer therapy effect.Chapter 1 is a brief introduction for the classification of nanocarriers,the construction of multifunctional mesoporous silica based drug delivery system and its applications in cancer therapy.In Chapter 2,a novel mesoporous organosilica-based pH-responsive drug delivery system is developed.pH sensitive polyacrylic acid(PAA)grafted MONs are first prepared via a facile grafting-to strategy and then cohesive glutathione(GSH)is conjugated on the PAA chain via amidation reaction with the amount of GSH up to 3,5wt%.The resultant MONs-PAA-GSH conjugate not only shows an excellent drug loading ability(with a high loading efficiency up to 43.75 ± 0.12%)but also pH-dependent release behaviors,which offers release efficiencies of 70.25%±0.87%(pH 3.0),45.51 ± 1.56%(pH 5.0)and 16.13±1.28%(pH 6.5),within 24 h.MONs-PAA-GSH shows an obvious enhanced uptake by the cohesive effect between GSH and cell membranes,resulting an enhanced therapeutic effect to cancer cells.In Chapter 3,on the basis of pH-response drug delivery system in the prior chapter,the capabilities of redox-response and imaging are further introduced to the nanocarriers.A self-fluorescent and dual-responsive drug delivery system is construct by incorporating acetaldehyde-modified-cystine(AMC)into MONs,shortly termed as MONs-AMC.Schiff base AMC contains two-C=N-bonds and a-S-S-bond which cleave in the presence of acidic medium and certain level of GSH,providing MONs-AMC-DOX the capability for triggering pH and GSH dual-responsive drug release.With 10 mmol L-1 GSH and pH 5.0,a drug release efficiency of 52.27±2.84%is achieved.Further,the self-fluorescent nature of MONs-AMC offers the tracing capability for imaging analysis in cancer cells,which facilitates the tracing and location of nanocarriers during drug delivery process.MONs-AMC-DOX exhibits an enhanced therapeutic effect to A549 cancer cells and provide a novel approach for exploiting efficient drug delivery vehicles.During the investigation in Chapter 3,the fluorescence intensity of AMC is increased upon the addition of thiols like GSH.In Chapter 4,a fluorescence enhancement sensing system based on this phenomenon is built for the detection of thiols,providing detection limits of 36 ?mol L-1 for GSH and 52 ?mol L-1 for cysteine(Cys)respectively.The sensing system is demonstrated to be stable in acid environment of cancer cell,and the fluorescence response of AMC is highly selective toward thiols in real biological matrixes.Considering the fact that GSH levels in cancer cells is significantly higher than those of Cys and other reducing species,the fluorescence enhancing response of AMC in cancer cells is dominated by GSH while the presence of small amount of Cys poses no effect.AMC is well demonstrated as a probe for selective intracellular GSH imaging in HeLa cells in this chapter.