| Cancer is a serious threat to human health and disease. According to the statistics of the United Nations World Health Organization (WHO), the incidence of cancer increased year by year because of the living environments, eating habits and so on. And in China, the annual number of deaths was around1.5million. However, the treatment of cancer was still difficult to overcome in medicine. Then, a series of chemotherapy drugs (doxorubicine, taxol, et al) with good efficacy were exploited and used in clinic. However, these drugs are mostly lack of specific pharmacological effects and exist serious side effects. This makes the patients treated with more physical burden, and drug bioavailability is very low. Thus, how to achieve efficient loading and controlled release of drugs has become a serious issue placed in front of the scientists and has become today’s focus in the biomedical research field. In this thesis, we fabricated a series of intelligent drug delivery system to resolve the problems such as low drug loading capacity, functionality limitations, and so on. Our approach has excellent biocompatibility and stability and could accumulate in tumor sites. Then, the drug carriers would trigger release the loaded drugs and finally cure the cancer.(1) Biocompatible and water-soluble magnetic nanoparticles with core (Fe3O4)-mesoporous shell (mSiO2) structure were prepared and successfully modified with the flourescent polymer chain as labeling segments and folic acid as cancer targeting moieties and loaded drug for directional release. The porous silica oxide structure and long molecular chains of polymethacrylic acid embedded drug efficiently in the nanocomposites and did not affect the magnetic properties of the carrier. Sustained release of the loaded drug was observed under in vitro conditions. Furthermore, the drug carrier is able to drill into the cell membranes and obtain a sustained release of anti-cancer drug in cytoplasm. The in vitro cellular uptake of drug demonstrated that the drug-loaded nanocomposites could effectively target to the tumor cells to cure it. Our model experiments indicated that the multifunctional mesoporous core-shell magnetic nanoparticle can be exploited as an anti-cancer drug delivery vehicle for targeting and therapy applications.(2) A water-soluble, pH-responsive copolymer was synthesized successfully and used as a polymeric-carrier to deliver hydrophobic paramagnetic nanoparticles into cells. In an acidic environment, the nanoparticles aggregate as the copolymer degrades, resulting in the enhancement of an in vitro MRI signal. A novel long-chain monomer was synthesized and then polymerized with a water-soluble monomer. The as-synthesized amphiphilic copolymer drug carrier has excellent biocompatibility and degradability properties. The hydrophobic copolymer side-chain can insert into the oleic acid with the hydrophilic part on the surface to form water-soluble nanocomposites. Furthermore, this composite can also easily load hydrophobic drugs via hydrophobic interactions. Degradation of the polymer shell under weakly acidic conditions leads to the release of the SPIONPs and drugs from the polymeric carrier, resulting in the MRI signal switching and drug release, respectively. Our approach can achieve these outstanding dual functions, tumor diagnosis and therapy.(3) Multifunctional drug delivery systems with favorable compatibility, high selectivity and efficiency are appropriate candidates for future medical applications. For this purpose, a multifunctional nanocomposite that enables selective magnetic resonance imaging and anticancer therapy by encapsulating hydrophobic superparamagnetic nanoparticles and chemotherapeutic agent doxorubicin with a novel biodegradable pH-activated polymeric carrier was synthesized. The as-synthesized amphiphilic polymer has excellent biocompatibility and pH-responsibility. The obtained nanocomposites selectively release the encapsulated drug and magnetic nanoparticles in mild acidic endosomal/lysosomal compartments due to the degradation of the pH-responsive bonds, resulting in a change of imaging signal and cancer therapy. Furthermore, when compared with the nanocomposites without targeting moiety, as studied from over-express the folic acid receptor tumor cell culturing, the conjugates with folic acid showed a significantly more potent targeting capability.(4) We fabricated a novel multifunctional nanocomposites consisting of hydrophobic HMSNPs and folate-conjugated amphiphilic capping agent for receptor-mediated controlled drug release. The first step was the synthesis of HMSNPs using polystyrene (PS) as template and tetraethyl orthosilicate (TEOS) as the Si source. Then the surface of HMSNPs was coated with a widely used fluorescent probe for optical imaging. The obtained fluorescent HMSNPs were modified with the long-chain hydrophobic moieties octadecyltrimethoxysilane (C18), which could change the wettability of the surface (from highly hydrophilic to hydrophobic), increase the amount of hydrophobic drug adsorption and further delay the drug release. The second step was the self-assembly of hydrophobic HMSNPs, drugs and folate-conjugated amphiphilic capping agent, which could effectively decrease clearance by reticuloendothelial system (RES), prevent drug carriers’aggregation, and interface with cellular uptake by steric hindrance. After the hydrophobic and van der Waals interactions between the alkyl chains (C18from hydrophobic HMSNPs and C12from amphiphilic capping agent), the hydrophobic drug could be loaded in HMSNPs and blocked by capping agent. The obtained multifunctional nanocomposites could be well dispersed in aqueous solution. When specifically recognized and internalized by folate receptor (FR) over-expressed tumor cells, the pH-responsive shell would hydrolyzed due to cleavage of acetal moieties in the weakly acidic endosomal/lysosomal compartments, resulting in loaded drug release. Thus, our approach can achieve these outstanding functions, tumor targeting, diagnosis and therapy.Based on the above works, we further studied the potential applications of hollow porous iron oxide and silica in lithium-ion anode materials.(5) Graphene-encapsulated ordered aggregates of Fe3O4nanoparticles with nearly-spherical geometry and hollow interior were synthesized by a simple self-assembly process. We combine the unique properties of graphene sheets and a hollow assembly of nanoparticles to simultaneously provide a large reversible Li+storage capacity, good rate performance and long cycle life. A simple self-assembly process driven by electrostatic interaction was used to generate graphene-encapsulated hollow Fe3O4nanoparticle aggregates (G-HM, short for graphene-encapsulated hollow magnetite particles). In this process, graphene oxide and HM nanoparticle aggregates were first modified to acquire negative and positive charged respectively. The assembly was carried out under very mild reaction conditions and consequently perturbations to the intrinsic properties of the HM nanoparticles could be kept to a minimum. The G-HM composite particles synthesized as such showed remarkable cycle stability as well as lithium storage performance compared to the pristine HM nanoparticles or a mixture of graphene and HM particles. The graphene modification of porous nanoparticle aggregates is therefore a viable and facile approach to prepare high performance anode materials for the lithium ion batteries.(6) We report a facile approach to fabricate monodisperse hollow porous Si (HPSi) nanoparticles (～120nm) via the magnesiothermic reduction of hollow porous SiO2(HPSiO2) nanoparticles formed by a templating method. This is followed by Ag nanoparticle coating for conductivity enhancement. The HPSi anode prepared as such shows several desirable electrochemical features:a high specific reversible capacity (3762mAh g-1), good cycle stability (>93%capacity retention after99cycles), and good rate performance (>2000mAh g-1at4000mA g-1), surpassing the performance of anode materials based on micron size macroporous Si particles. |
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