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The deadly nature of cancer and its rising prevalence globally have attracted plentiful studies. Non-invasive means of diagnosing and treating cancer have been among the top area of study. These methods have demonstrated high potential to excellently replace conventional approaches such as surgical excision and medical procedures such as chemotherapy, radiation therapy, or their combination. In addition to invasiveness, these methods solve the inability to remove all cancerous cells during surgery and inoperability related to adjacency to critical tissue structures. Among the non-invasive approaches, thermal medicine (including both diagnostics and therapeutics) has demonstrated promising advantages over conventional approaches owing to its simplicity, and potential applicability to tumours surrounded by vital human organs/regions that are not accessible using the conventional approaches. Nowadays, the deployment of gold-based nanostructures in photothermal therapy (PTT) is increasingly attracting and considered amongst the great achievements for cancer thermal medicine. Furthermore, investigation of novel biodegradable gold nanoparticles (AuNPs) is greatly desired especially for renal clearance, off-target toxicity, biocompatibility and high surface-enhanced Raman spectroscopy (SERS) signals.
This project is aimed at developing biodegradable noble metal nanoconstructs based on hybrid AuNPs and lipid templates (liposomes or lipid vesicles) with added SERS activity and PTT capability. Specifically, the work focuses on the optimisation of the AuNP fabrication according to contemporary protocols, assessment of the NP suitability for SERS application to cell samples, addition of specific ligands to the NP constructs for the investigation of SERS activity and validation of the NP’s response to PTT as the strategic way to achieve diagnosis and therapy within the same platform.
To study the effectiveness and potential of AuNPs and liposomes, this project employed a range of experimental techniques including Raman spectroscopy to study the structure, function and chemical composition of the gold nanoparticles (such as nanospheres and nanorods) and liposomes. The results from the synthesised AuNPs demonstrated the strongest SERS signals for 80 nm AuNPs with biphenyl-4-thiol (BPT) labelling, followed by 60 nm AuNPs labelled with 4-acetamidothiophenol (4-AATP). Also, the potential of liposome-encapsulated AuNPs for SERS and PTT applications was revealed under different considerations. Analytical techniques such as Transmission Electron Microscopy (TEM), PTT, Dynamic Light Scattering (DLS), UV-visible spectroscopy and stimulated Raman scattering (SRS) imaging were applied for the characterization of the novel nanohybrids in the context of cancer detection and treatment. The results of different protocols of nanohybrid synthesis revealed low toxicity for the 90-200 nm-sized unilamellar vesicle (ULV) based nanohybrids with small, 5 nm spherical AuNPs. The light-heat conversion efficiency of 5nm AuNPs+BPT+CTAB+liposome was also investigated by measuring their temperature rise over time during exposure to 808 nm laser radiation. According to our results, the 5nm AuNPs+BPT+CTAB+liposome constructs exhibits greater temperature increase over time, with an increase in PTT efficiency of 175.52% when compared with 5 nm AuNPs.
Additionally, the Raman spectral analysis of 5nm AuNPs+BPT+CTAB+liposome constructs
revealed the disappearance of two peaks at 1278 cm–1 and 1586 cm–1 due to the addition of CTAB, while largest enhanced factor was recorded at 1080 cm–1 for 5nm AuNPs+BPT+CTAB+liposome (8·105 counts) which can be effective for the diagnosis and treatment of cancer in the future.
In another development, the potential application of liposome-encapsulated gold nanorods (AuNRs) combined with SERS and PTT readouts was also investigated. Liposomes showed degradation above the membrane melting temperature (Tm) of around 42°C hence, following their integration in the nanoconstructs, they confer biodegradability by localized temperature increase above the Tm. Whilst small spherical AuNPs are difficult to arrange in larger constructs which exhibit plasmon resonance in the near-infrared (NIR) range, AuNRs have NIR absorption peaks that can be exploited in AuNRs+CTAB+liposome constructs with and without BPT labelling.
Overall, the research findings in this thesis will strengthen the development of novel Raman-labelled nanostructures for applications in nanotheranostics. The work will also open a way to the development of hybrid nanostructures for SERS-enabled diagnostics and laser-driven therapy using PTT. Finally, the cell disruption potential of gold nanostructures in non-invasive and biocompatible ways will be established. |
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