Silicon-Based Nanocomplex For Novel Photo-induced Combined Cancer Therapy

Traditional tumor treatment methods such as radiotherapy,chemotherapy,and surgical resection have some deficiencies.For example,radiotherapy lacks selectivity for tumor tissue and normal tissues;chemotherapy is prone to drug resistance;surgical resection is not effective for metastatic lesions.Therefore,there is an urgent need to develop new methods of cancer therapy.In recent years,nanomaterials have been widely used in the novel tumor treatments due to their unique optical,magnetic,acoustic,X-ray absorption,and catalytic properties.In the process of tumor growth,owing to the rapid proliferation of tumor cells,changes in metabolic pathways and malformations of tumor blood vessels,solid tumors often have a series of microenvironment characteristics different from the normal tissues,such as hypoxia,slightly acid,overexpressed hydrogen peroxide(H2O2),and high glutathione(GSH),which often lead to the failure of tumor treatments.Therefore,it is necessary to develop new functional nanomaterials to regulate tumor microenvironment(TME)and improve the effect of tumor treatments.Silicon nanowires(SiNWs)have strong optical absorption in the near-infrared region.The silicon-hydrogen bonds formed on the surface after being treated with hydrofluoric acid(HF)have good catalytic effects,and silicon itself has the good biocompatibility,which will play an important role in the tumor diagnosis and treatment.In this thesis,three kinds of silicon-based nanocomposites with the function of regulating TME are mainly constructed based on SiNWs,and the research of combined cancer therapy is also carried out.The main contents are summarized as follows:Chapter 1:The applications of nanomaterials in the new tumor treatment strategies were summarized.The research progress of silicon-based nanomaterials in the field of biomedicine and the role of nanomaterials in the regulation of TME were introduced.Finally,the basis for selecting the topic and the research content of the paper were described.Chapter 2:The nanocomposites of Au nanoparticles-loaded silicon nanowires for near-infrared photothermal therapy and photoacoustic imaging:Hydrofluoric acid-treated SiNWs had strong reduction effects.Au nanoparticles could be accurately grown on the surface of SiNWs by in situ reduction to construct Si-Au nanocomposites.Si-Au nanocomposites had good absorption in both the first near-infrared(NIR-Ⅰ)region and the second near-infrared(NIR-Ⅱ)region.Using absorption in the NIR-Ⅰ region,photoacoustic(PA)imaging could be performed.Utilizing their absorption in the NIR-Ⅱregion,photothermal therapy(PTT)in the NIR-Ⅱ region could be conducted.Therefore,Si-Au nanocomposites had important research prospects of PTT in the NIR-Ⅱ region under the guidance of PA imaging.Chapter 3:The nanocomposites of Pt nanoparticles-loaded SiNWs for photothermal enhanced chemodynamic/sonodynamic therapy:Pt nanoparticles were reduced on SiNWs by in situ reduction,and then modified on the surface with polyethylene glycol thiol(PEG-SH)to prepare Si-Pt nanocomposites with good biocompatibility.The nanocomposites could convert excess H2O2 in the TME into active oxygen radicals and had the effect of chemodynamic therapy(CDT).At the same time,they could generate active oxygen species(ROS)under the ultrasound(US)condition and had the effect of sonodynamic therapy(SDT).Due to the structure of SiNWs,the CDT and SDT effects of Si-Pt nanocomposites were stronger than those of pure Pt nanoparticles.In addition,the mild photothermal effect of the nanocomposties themselves further improved the chemodynamic/sonodynamic activity and realized the combined tumor treatment effect Therefore,Si-Pt nanocomposites had the effect of photothermal enhanced chemodynamic/sonodynamic combined therapy,and played an important role in the new tumor treatments.Chapter 4:The nanocomposites of Cu nanoparticles-loaded SiNWs for glutathione(GSH)depletion and photothermal enhanced chemodynamic therapy:Si-Cu nanocomposites were constructed by in situ reduction.Based on the catalytic activity of Cu nanoparticles,Si-Cu nanocomposites could convert H2O2 into ROS and had the effect of CDT.At the same time,the good optical absorption in the near-infrared region of the nanocomposites could be used for mild photothermal effect to enhance CDT.In addition,Si-Cu nanocomposites also had strong GSH depleting ability,which could further amplify the tumor therapeutic effect of ROS.In this paper,the applications of nanomaterials in the new tumor treatment strategies and the research progress of silicon-based nanomaterials in the field of biomedicine were outlined,the focus was on the application of silicon-based nanocomposites based on the regulation of TME in the combined cancer therapy.The research results provided the ideas and methods for the application of functional silicon-based nanocomposites in the new tumor treatments.