Surface and composite engineering of iron oxide nanoparticles (IONPs) for biomedical applications

Abstract

Magnetic iron oxide nanoparticles (IONPs) have attracted particular research attentions for a wide range of biomedical applications. For biomedical applications, it is essential to develop surface engineering strategies for IONPs to achieve water solubility, to prevent aggregation, to chemically stabilize them against degradation, and to achieve further functionality for biomedical applications. Besides engineering the surface of each single nanoparticle, IONPs can also be used as fundamental building blocks for fabrication of composite materials. By varying the composition of the involved materials and spatial arrangement of IONPs, the physical and chemical properties of the IONP-containing composite materials can be tailored to meet different requirements. Part I of this thesis introduced the research background, research motivation, and organization of this thesis. Firstly, it was introduced that why the IONPs are desirable for biomedical applications and what advantages they possess. Then the synthesis methods of IONPs, surface engineering strategies of IONPs, and IONP-containing composite materials were reviewed. The motivation of study biotin and silica for engineering of IONPs were introduced. Finally, the organization of this thesis was summarized. The main research works were introduced in two parts: Part II, biotin engineered IONPs; and Part III, silica engineered IONPs. In Part II, IONPs were synthesized by thermal decomposition. For surface engineering of IONPs, a surfactant addition method was used and biotinylated IONPs (biotin-IONPs) were prepared. Taking advantages of the biotin moieties on their surfaces, biotin-IONPs can work as magnetic labels for magnetic biodetection. A magnetic immunoassay for AFP was developed using 15-nm biotin-IONPs. Subsequently, by applying this magnetic immunoassay on GMR sensor (GF708) surfaces, a magnetic biodetection platform was developed. Moreover, since each streptavidin molecule can provide four binding sites for biotin, the multi-binding of biotin-IONPs with streptavidin-detection antibodies (Abs) was realized. This gave biotin-IONPs a chance to improve the sensitivity of magnetic biodetection technologies. In addition, the biotin-avidin interaction can be broken by a brief exposure to 70℃ deionized (DI) water. Based on this property, a binding-releasing strategy was developed to decrease the influence of nonspecific bound biotin-IONPs. Besides working separately as magnetic labels, utilizing avidin-induced cross-linking method, the biotin-IONPs were synthesized into different types of assemblies. These biotin-IONP assemblies were promising candidates for MRI contrast agents or magnetic drug delivery system. In Part III, silica was studied for engineering of IONPs. As to surface engineering, silica encapsulated IONPs were synthesized as a potential MPI tracer material. As to synthesis of composite materials, silica coated IONP clusters and IONP-hollow mesoporous silica sphere (IONP-HMSs) composite were synthesized. The silica coated IONP clusters provided a substrate for attachment of protein corona, and a facile nanoparticle immunoassay was developed. The hollow morphology of IONP-HMSs composite made it promising candidate for magnetic drug delivery. Finally, in Part IV, the unique properties and corresponding advantages of biotin and silica were summarized. The studies of biotin and silica engineered IONPs opened new horizons for the biomedical applications of IONPs, and may revolutionize the healthcare practices in the future.