Multifunctional Metal Oxide/Sulfide Nanostructures For Cancer Theranostics

In recent years,with the rapid development of nanotechnology,the application of nanomaterials in the biomedical field has drawn great attention.Due to their unique physicochemical properties,nanomaterials have been widely applied for drug delivery,bioimaging,optical therapy,radiation therapy and so on.In addition,with highly integrated functionalities,the imaging information offered by nanomaterials may be employed for the better design of therapeutic plans.However,the biological safety of nanomaterials remains a great concern so far due to their prolonged body retention.Their potential toxicological effect will greatly hinder the development of nanomaterials for biomedical applications.Therefore,it would be of great significance to explore biodegradable multifunctional nano-agents for cancer theranostics.In this thesis,we fabricate two kinds of multifunctional metal oxygen/sulfide nanostructures for novel tumor theranostics.The main results are as follows:Chapter 1: In this chapter,the recent research progresses regarding biomedical applications of metal oxygen/sulfide nanostructures would be introduced.The in vivo degradation behaviors and toxicology studies of nanomaterials,especially metal oxygen/sulfide nanomaterials,would then be discussed.Chapter 2: In this chapter,we fabricate mesoporous tantalum oxide(m Ta2O5)nanoparticles with polyethylene glycol(PEG)modification.Those m Ta2O5-PEG nanoparticles with the mesoporous structure and high surface area can serve as a drug delivery vehicle to allow efficient loading of chemotherapeutics such as doxorubicin(DOX),whose release appears to be p H-responsive.Meanwhile,owing to the interaction of Ta with X-ray,m Ta2O5-PEG nanoparticles offer an intrinsic radio-sensitization effect to increase X-ray-induced DNA damages during radiotherapy.As the results,DOX loaded m Ta2O5-PEG(m Ta2O5-PEG/DOX)nanoparticles are able to offer strong synergistic therapeutic effect for both in vitro and in vivo experiments during the combined chemo-radiotherapy.Furthermore,such m Ta2O5-PEG/DOX shows remarkably reduced side effects,which can be useful for the delivery of safe and effective chemo-radiotherapy.Chapter 3: In this chapter,we develop metabolizable vanadium sulfide nanostructures for biomedical applications.As-made VS2 nanosheets upon ultrasonication and lipid modification can be converted into ultra-small VS2 nanodots encapsulated inside polyethylene glycol(PEG)modified lipid micelles.Owing to the paramagnetic property and strong near-infrared region(NIR)absorbance of VS2,such VS2@lipid-PEG nanoparticles can be utilized for in vivo T1-weighted magnetic resonance(MR)imaging and photoacoustic(PA)imaging.Moreover,labeled with 99mTc4+ upon simple mixing,VS2@lipid-PEG nanoparticles are also applied for Single-Photon Emission Computed Tomography(SPECT)imaging.With all those functions together,in vivo multimodal imaging guided photothermal tumor ablation treatment can be realized with great efficacy.Importantly,along with the gradual degradation of VS2,VS2@lipid-PEG nanoparticles exhibit effective body excretion without appreciable toxicity to the treated animals.This biodegradable nanostructure shows great promise for applications in cancer theranostics.To summarize,two types of metal oxide/sulfide nanostructures are fabricated in this thesis and ultilized for applications in drug delivery,biomedical imaging and cancer combination therapy.It is hoped that our results would provide useful information to guide the design of other interesting functional nanostructures for nanomedicine and cancer theranostic applications.