Polymer-QD hybrid nano-theranostics for Glioblastoma Multiforme treatment

该博士学位的主要目的是开发一种替代方法，用于设计和制造多形性胶质母细胞瘤（GBM）的治疗药物全身共递送系统，从而提高目前使用的标准难溶性药物在GBM治疗中的效率。这将通过采用纳米级CQD来实现，通过逐层组装（LbL）形成具有治疗药物的纳米胶囊，用于靶向药物递送成像。LbL的过程是确保纳米涂层将嵌入抗癌药物，然后一旦在靶位点提供药物的运输和随后的控制释放。这个博士学位将涉及许多不同的阶段，以实现一个全新的治疗目标。第一阶段将是了解治疗递送系统如何工作，它们如何对癌细胞起作用，并确定需要哪些治疗药物来靶向这些癌性肿瘤细胞。这将有助于给出该疾病的总体分子图谱和治疗策略。在此之后，下一阶段将是充分了解CQDs是如何形成的。这将需要研究来自碳基材料的CQD的性质，这些性质对于用于治疗药物递送是理想的。将进行测试，以确定最有效和高产的方式来获得CQDs，例如从生物质废物中获得，如果这是以最简单，最便宜，最安全的方式产生CQDs的方法。将对CQD产品进行几项测试，以确保它们适合继续进行，其中包括SEM-EDX、TEM、FTIR、TGA、XRD、XPS、BET、AFM，这些是一系列测试技术，以优化和优化制造条件，同时将使用GC和GC/MS（气体在线和液体离线）分析气体和冷凝液体产品。生成的多孔碳材料将用不同的化学品进行改性，以获得优化的所需性能和更好的机械强度。功能化材料将基于使用BET的孔径分析、使用CNHS分析仪的碳-氮-氢-硫含量、使用FE-SEM、XRD、FTIR、XPS和拉曼光谱法的材料形态和结构进行表征和优化。电化学性能将在电化学电池中进行表征，以测试其电容和电化学活性。随后，将研究LbL组装，并确定其优于先前用于生成沉积多层膜的尝试的原因。这将使药物递送系统能够在纳米级上功能化。这将有助于了解它们如何在特定的治疗药物周围形成外壳。这将需要理解CQD与药物分子的化学位点/结构之间产生的化学相互作用/键。一旦确定了这一点，CQDs和治疗药物就可以一起反应，得到药物传递系统所需的整体结构。本博士项目将从背景和该领域的现状分析中回答以下研究问题：1.了解CQD的发光以及波长/颜色的差异如何影响纳米诊断学2。如何从纳米胶囊中释放药物/控制释放，即成功且不过早3。使用不同的癌症药物，将研究是否CQDs将有不同的功能组4。药物的运输是否需要保护基化学？5.研究CQDs对健康和肿瘤细胞的影响6. GBM癌区的成像7.生物屏障反应，需要看到的路线，nanotheranostics将采取8.血流如何影响治疗输送？9.如何延长CQDs的使用寿命

The main aim of this PhD will be to develop an alternative approach for the design and manufacture of a therapeutic drugs systemic co-delivery system for Glioblastoma Multiforme (GBM), hence enhancing the efficiency of currently used standard poor soluble drugs applied in GBM therapy. This will be achieved by employing nanoscale CQDs, forming a nano-capsule with the therapeutics drugs by Layer-by-Layer assembly (LbL) for targeted drug delivery imaging. The process of LbL is ensuring that a nano-coating layer will embed the anticancer drugs and then provide transport and subsequent controlled release of the drug once at the target site. This PhD will involve many different stages to achieve an overall new therapeutic target. The first stages will be to understand how therapeutic delivery systems work, how they work for cancer cells and to establish which therapeutic drugs are needed for targeting these cancerous tumour cells. This will help to give an overall molecular map and therapeutic strategy of the disease. Following this, the next stage will be to understand fully how CQDs form. This will require research into the properties of CQDs derived from carbon-based material that are desirable for the use in therapeutic drug delivery. Tests will be performed to determine the most efficient and high yielding way to obtain CQDs, such as from biomass waste, should this be the method which generates CQDs in the most facile, cheapest safest way. Several tests will be performed on the CQD product to ensure they are appropriate for moving forward, which include SEM-EDX, TEM, FTIR, TGA, XRD, XPS, BET, AFM, which are an array of testing techniques in order to characterise and optimise the fabrication conditions, while the gas and condensed liquid products will be analysed using GC and GC/MS (on-line for gas and off-line for liquid). The porous carbon material generated will be modified with different chemicals to give optimised desired properties and better mechanical strength. The functionalised material will be characterised and optimised based on pore size analysis using the BET, carbon-nitrogen-hydrogen-sulphur content using the CNHS analyser, material morphology and structure using the FE-SEM, XRD, FTIR, XPS and Raman Spectroscopy methods. The electrochemical properties will be characterised in electrochemical cells for testing their capacitance and electrochemical activities.Following this, LbL assembly will be studied and the reasons that it overrides previously used attempts at generating deposited multilayers will be established. This will enable functionalisation of the drug delivery system at the nanoscale. This will help to understand how they'd form a shell around the specific therapeutic drugs. This will require understanding the chemical interactions/ bonds that arise between the CQDs and the chemical sites/structure of the drug molecules. Once this is determined, the CQDs and the therapeutic drugs can be reacted together to give the overall structure necessary for a drug delivery system.From the analysis of the background and the current state of the art of the field, this PhD project will give an answer to the following research questions: 1. Understand the luminescence of the CQDs and how difference in wavelength/ colour will affect the nanotheranostics2. How to release the drugs from the nano-capsule/ controlled release i.e. successfully and not too early3. The use of different cancer drugs, will study whether the CQDs will have to differ in terms of functional groups 4. Will Protecting Group Chemistry be needed for the transport of the drugs?5. Study the effect of CQDs on the healthy and tumoral human cells6. Imaging of the GBM cancer area7. Biological Barriers Reaction, need to see the route that the nanotheranostics will take8. How is the therapeutic delivery affected by the bloodstream? 9. How to expand the lifetime of the CQDs