Developing polymer-based upconverted nanoparticles for cell stimulation

该项目旨在开发一种基于脂质的纳米颗粒系统，该系统具有共轭聚合物的功能，可以作为上转换的生物兼容纳米颗粒。这些将被用作一种系统，将近红外(NIR)转换为电刺激，可用于释放药物有效载荷和/或以非原位方式刺激神经元动作电位。免疫反射弧的发现正在给医学带来革命性的变化，因为现在人们在通过调节神经元中继来治疗疾病方面做出了巨大的努力。例如，在调节迷走神经方面，现在正在开发新的治疗方法来治疗一系列疾病，从与免疫相关的疾病，如关节炎和肠易激综合征，到血压、糖尿病等。重要的是，最近发现胶质瘤通过与癌细胞的电子通讯与神经细胞进行电子通讯，从而促进肿瘤的发展，为胶质瘤的治疗开辟了新的领域。这样做的首选标准是通过电子设备的植入性包裹，由于其侵入性和定期更换的需要，这限制了其作为治疗选择的广度。目前，在开发以无线方式刺激神经元通路的新工具和材料方面存在挑战，这是本博士试图解决的问题。因此，迫切需要新的面向外部的刺激工具，以消除这种治疗的侵入性。为了实现这一目标，我们计划制造聚合物功能化上转换纳米颗粒，它可以将光转换为电输入，以驱动细胞的行为。这些纳米粒子将与神经细胞相连，当受到近红外光(能够穿透组织深处)刺激时，可以驱动局部电位变化，这可以通过两种方式使用，要么用于直接刺激神经元继电器，要么通过释放或获得抑制或增加神经元刺激的药物。这项技术通过提供一种无线神经刺激方法，拓宽了多种疾病的基于神经元的治疗方法。

The project aims to develop a lipid-based nanoparticle system functionalised with conjugated polymers to act as upconverted biocompatible nanoparticles. These will be used as a system to convert near infrared (NIR) to an electrical stimulus that can be used to release a drug payload and/or stimulate neuronal action potentials in an ex-situ manner. The discovery of the immune reflex arc is revolutionising medicine as there are now huge efforts in treating disease by modulating neuronal relays. For example, in modulating the vagal nerve there are now new treatments being developed to treat a host of diseases from immune-related disorders such as arthritis and irritable bowel syndrome through to blood pressure, diabetes and many more. Importantly, it was recently discovered that gliomas electrically communicate with neuronal cells to advance tumour progression by electrically communicating with cancer cells, opening up new scope to treat gliomas. The go-to standard in doing this is through implantable wrap around electronics which limits its breadth as a treatment option due to its invasiveness and need for regular replacement. There is currently a challenge in developing new tools and materials for stimulating neuronal pathways in a wireless manner which this PhD seeks to address. Therefore, there is a pressing need for new externally facing stimulation tools that would negate the invasiveness of such treatments. To achieve this, we plan on fabricating polymer functionalised up-converted nanoparticles which can convert light into electrical inputs to actuate the cell's behaviour. These nanoparticles will be interfaced with neuronal cells and when stimulated by NIR light (capable of penetrating deep in the tissue), can drive local potential changes which can be used in two ways, either for direct stimulation of neuronal relays or through the release or availability of drugs that inhibit or increase neuronal stimulation. This technology offers to broaden neuronal-based treatments of multiple diseases by offering a wireless approach to neuronal stimulation.