Abstract
The main objective of this dissertation is to design, prepare and evaluate the potential biomedical application of peptide-based hybrid functional biomaterials. Synthetic biomaterials have attracted much attention due to their well-controlled constituents and structures, highly tunable physicochemical properties and good biocompatibility. They have therefore found a wide range of biomedical applications, including diagnosis, drug delivery, surgery, tissue engineering, etc. Peptides, which are short chains of amino acids linked by peptide bonds and serve as one of the basic units for biological systems, have emerged as excellent candidates for biomaterials because of their versatile structures, programmable and ready synthesis, varied bio-functionality, excellent biocompatibility and biodegradability. Incorporation of peptide and synthetic nano-materials can potentially combine the advantages of precise chemical structure and diverse functionality of biomolecules with the stability and processibility of artificial nano-materials, resulting in materials with synergic or novel properties.Chapter 1 serves as an introduction to nanomaterial and peptide, with a focus on their application in biomedical science. Nanotechnology has been burgeoning in the past decades, and emerged as powerful new tool for biological or biomedical research, including cellular labeling, imaging, sensing, theranostic materials, and drug delivery. On the other hand, peptides are biological inherent expression language and show the advantage of outstanding biocompatibility, making them highly promising to provide a functional interface for nano-materials. And what's more, they also exhibit versatile bio-functionality, making themselves ideal bio-material for biomedical applications. This chapter will give an overview of the development of various nanomaterials and their applications, particularly in biological and biomedical area. It will also introduce some fundamental information about peptide, including general structures and synthesis of peptides, and development of peptide based bio-materials applied in tissue engineering, biological sensing, disease diagnosis and therapy, etc. Inspired by the elucidation of the fundamental features and exploration of applications of nanomaterials and peptides, we aimed to design and synthesize some stimuli-responsive peptide-based bio-nanomaterials applied for biomarker sensing or controlled drug delivery, by incorporating rationally designed peptide and nanoparticles or self-assembly of amphiphilic peptide.
In Chapter 2, we describe a modularly designed colorimetric platform for facile detection of proteases with high sensitivity and selectivity. The strategy takes advantage of peptide induced aggregation of gold nanoparticles upon cleavage by specific proteases, which results in loss of negatively charged stabilizing factors in the peptide, causing aggregation of gold nanoparticles and a visible color change from wine-red to purple or even blue. This method allows a facile visual assay of the enzyme activity without any sophisticated instrument, affording improved simplicity and throughput, while quantitative assay can be performed when a UV-Vis spectrophotometer is employed. Additionally, the use of synthetic peptide with high purity and appropriate length to recognize enzyme of interest could offer improved specificity as compared with existing techniques based on natural macromolecules. Furthermore, this design can theoretically be utilized for detection of any protease just by replacing the substrate peptide sequence for specific enzyme.
Chapter 3 reports the design, synthesis and testing of a hierarchical nano-vehicle for targeting delivery of anti-cancer drugs to cancerous cells. In this nano-carrier, peptides coated gold nanoparticles were employed as nano-valve for mesoporous silica nanoparticles (MSNs) to construct stimuli-responsive drug delivery system (DDS) with bio-active surfaces. MSNs were functionalized with acid-labile α-amide-β-carboxyl groups to carry negative charges, and capped with positively charged gold nanoparticles that were functionalized with oligo-lysine containing peptides. The hybrid delivery system exhibited endo/lysosomal pH triggered drug release and incorporation of RGD peptide facilitated targeting delivery to cancer cells that over-express αvβ3 integrin. Such system is expected to serve as a platform for preparation of diversified multi-functional nanocomposites with various functional inorganic nanoparticles and bioactive peptides.
Chapter 4 describes the design and preparation of a short peptide based hydrogel that is responsive to hydrogen sulfide (H2S). H2S is an important gaso-transmitter whose deregulation has been associated with a number of pathological conditions. The hydrogel design is based on the functionalization of an ultra-short hydrogelating peptide sequence with an azidobenzyl moiety, which was reported to react with H2S selectively under physiological conditions. The resulting peptide was able to produce hydrogels at a concentration as low as 0.1 wt%. It could then be fully degraded in the presence of excess H2S. As-prepared hydrogel developed in this study may provide useful tools for biomedical research.
Finally, Chapter 5 provides a brief summary of this dissertation, by pointing out the advantages of peptides and nanomaterials as candidates for biomaterials based on their promising properties. It also highlights that some challenges within this new generation materials should be noted. Greater effort is required to conduct in-depth and systematic study for better understanding of the essence, which is critical for overcoming the barriers and manipulating the novel materials.
| Date of Award | 22 Jul 2016 |
|---|---|
| Original language | English |
| Awarding Institution |
|
| Supervisor | Hongyan SUN (Supervisor) |