Delivery of various drugs and biomolecules into cells is crucial in modern medicine, providing promising potential in the treatment of incurable diseases. Most naked therapeutic biomolecules, for example, proteins, siRNAs and some free drugs can hardly penetrate into cells, thus various natural particulates and synthetic vectors have been used as cellular delivery vehicles. The understanding of structure-function relationships of natural particulates provides a useful guide for the design of new nanocarriers with better safety and higher delivery efficiency. Currently, many research attempts have focused on the synthesis of new drug delivery systems by mimicking the advantages of enveloped viruses, which have evolved sophisticated mechanisms that make use of or shield off cellular signalling and transport pathways to traffic within host cells and deliver cargos into appropriate subcellular compartments. However, there are still some parameters of enveloped viruses requiring intensive study, for example, the contribution of viral surface topography (rough surface) to intracellular delivery of cargo molecules.This thesis focuses on the development of a novel drug delivery system with high performance based on the preparation of silica nanoparticles with virus-mimicking rough morphology and gains insight into the roles of surface roughness variation and surface functionality (e.g. polyethylenimine and octadecyl-group) in biomolecule (e.g. siRNAs and therapeutic proteins) delivery performance.The main achievements obtained in this thesis are listed below.In the first part, a new and facile approach has been developed to prepare the virus-mimicking silica nanoparticle (VMSN) with a rough surface. We show that increases in nanoscale surface roughness promote both binding of biomolecules (e.g., genetic molecules) and cellular uptake; thus, the cargo delivery efficiency is significantly increased, regardless of surface functionality and cell types.Finally, gene delivery efficiency was tested, where the biomimetic nanoparticles shows a better cell growth inhibition performance than the smooth silica nanoparticle and a commercial delivery reagent.In the second part, the novel and facile approach for systematically controlling surface roughness of silica nanoparticles has been developed. Based on our "neck-enhancing" approach, rough silica nanoparticles (RSNs) with a fixed core particle (211 nm in diameter) and varied shell particles are obtained. The increase of shell particle s z s rom 13 to 98 nm enlarges interspacing distance tw n n our n s ll p rt l s rom 7 to 38 nm, where protein molecules will favourably absorb onto one of RSNs without impacting protein binding ability.
Publications included in this thesis1. Yuting Niu, Amirali Popat, Meihua Yu, Surajit Karmakar, Wenyi Gu and Chengzhong Yu.Recent advances in the rational design of silica-based nanoparticles for gene therapy.