Silicon Nanomaterials-Based Bioimaging, Disease Diagnosis And Therapy

Silicon is the crust’s second most abundant element, which provides inexpensive and plentiful resources for low-cost and large-scale fabrication of silicon-based nanostructures. The as-prepared silicon nanostructures, especially 1-dimensional silicon nanowires(SiNWs) and 0-dimensional fluorescent silicon nanoparticles(SiNPs), have attracted great attentions for applications in various fields, such as energy, catalysis, biology and biomedicine, due to their attractive advantages(i.e., excellent physicochemical/optical/electronic properties, favourable biocompatibility, surface tailorability, and so forth). Furthermore, in comparation with other nanostructures(i.e., metal-based nanostructures(gold nanostructures, siliver nanostructures, et al.), semiconductor II-VI quantum dots, carbon-based nanomaterials, and so forth), the previous work has shown that silicon nanomaterials can be biodegradable into low-toxicity or non-toxicity products cleared via renal clearance, which motivated the investigation of silicon nanomaterials for various bioapplications. Moreover, huge surface-to-volume ratios of silicon nanomaterials offer great opportunities for drug loading or biomoleculars modification, which open a new way for design of high-performance silicon-based multifunctional nanoagents and nanoprobes for bioimaging, disease diagnosis and therapy.In this dissertation, utilizing SiNWs and SiNPs with attractive merits synthesized by our group, we further investigate the nanobio interactions between cellular and silicon nanostructures, the applications of silicon nanomaterials for disease diagnosis and treatment, which show the unique advantages of silicon nano-biotechnology. The main research results are as follows:Chapter 1: In this chapter, we review the recent research progresses of silicon nano-biotechnology, and discuss the motivations of research in this dissertation.Chapter 2: Doxorubicin(DOX)-loaded silicon nanowires(SiNW-DOX) for the treatment of drug-resistant cancer cells. In this chapter, we develop a novel SiNW-based nanocarrier with high-efficacy for treatment of drug-resistant breast cancer cells. Compared with high resistant factor(RF) treated with free DOX or other nanomaterials-based nanocarriers, the RF value of SiNW-DOX is as low as ~2.0. Considering that SiNWs can be prepared in a facile, reproducible and low-cost route, such SiNW-based nanocarriers hold great promise for cancer therapy, especially for the drug-resistance cancer cell lines.Chapter 3: Silicon nanowires-based therapeutic agents for in vivo tumor near-infrared photothermal ablation. Gold nanoparticles(AuNPs)-decorated SiNWs are employed as high-performance near-infrared(NIR) hyperthermia agents for highly efficacious in vivo tumor ablation. Significantly, the overall survival time of SiNWs-treated mice is drastically prolonged, with 100% of mice being alive and tumor free for 8 months, which is the longest survival time ever reported for tumor-bearing mice treated with nanomaterials-based NIR hyperthermia agents.Chapter 4: DNA aptamers self-assembly of targeted silicon nanoparticles as novel theranostic probes for synchronous bioimaging and chemotherapy. By conjugating SiNPs with MUC-1 DNA aptamers, which have three major prerequisities: specific cell targeting, drug loading, and controlled release of drug triggered by an endogenous stimulus, we present a multifunctional SiNP-based theranostic probe for targeted bioimaging and anticancer treatment. Upon reaching endo/lysosomes of targeted cancer cells via receptor-mediated endocytosis, the intracellular nucleases will contribute to the degradation of DNA aptamers, facilitating the release of active drug molecules(DOX). Such released DOX molecules thereafter permeate through intracellular milieu, eventually reaching cellular nuclei and intercalating between DNA base pairs to kill targeted cancer cells exclusively.Chapter 5: Hydrophilic silicon nanoparticles inhibit migration of human retinal endothelial cells(HRECs) by affecting cytoskeleton. In this chapter, carboxyl- and amine-terminal SiNPs(denoted as SiNPs-COOH and SiNPs-NH2, respectively) are synthesized to provide negative and positive surface SiNPs, and performed as migration inhibitors in HRECs. In our investigation, both kinds of SiNPs can effetively inhibit cellular migration without obvious cytotoxicity. Especially the inhibition of migration by SiNPs-NH2 is stronger than that of SiNPs-COOH, due to SiNP-NH2-mediated massive disruption of cellular cytoskeleton assembly.In summary, this thesis demonstrates a comprehensive investigation of SiNW- and SiNP-based nanoprobes for bioimaging, disease diagnosis and therapy, i.e., drug-resistant cancer cells’ treatment, near-infrared photothermal ablation of tumor in vivo, synchronous bioimaging and chemotherapy of MUC-1 targeted cancer cells, and the influence of HRECs’ migration. Our results greatly offer a new platform for further applications of those silicon nanomaterials in biomedical research.