Silicon-Based Multifunctional Nanomaterials For Combined Treatment Of Cancers

With the rapid development of nanotechnology,nanomaterials have been widely utilized as drug delivery carriers for the combined cancer therapy.In this dissertation,taking advantage of unique optical/electrical properties of silicon nanomaterials,we have designed and constructed multifunctional silicon-based drug/gene nanocarriers for combined treatment of drug-resistant cancer cells.The detailed research contents and results are briefly described as follows:Chapter 1: In this chapter,the current research progress of combined cancer therapy is briefly introduced,and then synthetic methods of silicon-based nanomaterials and their research progress in the field of cancer therapy are further illustrated.Finally,we discuss the basis,objectives,and methods of the study in this dissertation.Chapter 2: In this chapter,we systematically investigate the construction of one new type of multifunctional silicon nanowires（MFSi NWs）and their application in photothermal-chemotherapy combination treatment of cancer cells.Due to large specific surface area and tailorable surface modification of silicon nanowires（Si NWs）,gold nanoparticles and ferroferric oxide nanoparticles are decorated on the surface of Si NWs,producing multifunctional Si NWs nanohybrids.Notably,the as-prepared Si NWs nanohybrids simultaneously feature three functions:（1）high drug loading capacity of doxorubicin（DOX）molecules(²000 mg g^-1);（2）distinct photothermal,i.e.,temperature increases by 40 o C after a short-time（⁵ min）irradiation under 808 nm laser at low power density(e.g.,1 W cm^-2);（3）magnetically responsive drug delivery,i.e.,significantly enhanced cellular uptake of DOX（⁶5% higher than control groups without magnetic treatment）could be observed under magnetic treatment.Taking advantage of these unique merits,drug-resistant cancer cells could be effectively destructed.Chapter 3: In this chapter,we focus on the preparation of multifunctional silicon nanoparticles（MFSi NPs）and their application in image-guided chemo-gene therapy of drug resistant cancer cells.The MFSi NPs could protect small interference ribonucleic acid（si RNA）from degradation with p H/phosphate-responsive behavior.The results of live-cell tracking reveal that the intracellular releasing behaviors of si RNA and DOX molecules are time-dependent,i.e.,si RNA is rapdly released within a relatively short time（⁶ h）,while DOX molecules are gradually released during a long-time incubation（²4 h）.Real-time polymerase chain reaction（RT-PCR）and immunofluorescence staining indicate that the complex could efficiently down-regulate the expression of P-glycoprotein messenger RNA（m RNA）and P-glycoprotein in 48 h（⁸0% off）.Efficacy test suggests that the multidrug resistance of human breast cancer cells could be effectively reversed,and the half-inhibitory concentration（IC50）of DOX in the complex decreases to 3 μg m L-1,which is much lower than that of free DOX group（¹12 μg m L-1）.In summary,this thesis presents a comprehensive investigation on silicon-based multifunctional nanosystem for combined treatment of cancer cells.The above-mentioned results offer a new platform for further promoting the application of nanomaterials in the field of cancer therapy.