Modelling of Prodrug Conversion Through Palladium Nanoparticles Encapsulated in Polymers

通过封装在聚合物中的钯纳米颗粒进行前药转化的建模

基本信息

批准号：
2894749
负责人：
金额：
--
依托单位：
Heriot-Watt University
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2023
资助国家：
英国
起止时间：
2023 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2894749
关键词：
Modelling Prodrug Conversion Through Palladium

项目摘要

Most anti-cancer drugs have serious side effects, limiting their efficacy. These could be reduced by using a prodrug which circulates harmlessly until being activated at the tumour site. In this project, we present a biophysical research programme comprising a experiments and an in silico model that aims to develop prodrug treatment strategy for multi-drug cancer therapies and chemical modulation of cancer cells. This work is based on the conjecture that designing and tailoring catalyst (palladium) embedded implants can provide a controlled prodrug-to-drug conversion near cancer cells. We will develop the polymer implants encapsulating palladium (Pd) and test its efficacy of prodrug diffusion, reaction, and conversion in quasi-2D and 3D experiments. In parallel work, we intend to develop a reliable and accurate in silico (mathematical and computational) model of prodrug conversion and validate its predictions with experiments. The validated model will be used as a "computer-aided design platform" to inform the design of experiments as well as the development of implants. We foresee that this whole framework will assist clinicians and practitioners to screen their prodrug strategies for desirable/non-desirable properties, thereby reducing the cost of laboratory-scale experimentation, accelerating development and hence the commercialisation of clinically relevant forms of Pd-bearing implants.

大多数抗癌药具有严重的副作用，从而限制了其功效。可以通过使用无害循环直到在肿瘤部位激活的前药来减少这些方法。在该项目中，我们提出了一个包括实验和硅模型中的生物物理研究计划，该计划旨在制定用于多药癌疗法和癌细胞化学调节的前药治疗策略。这项工作是基于猜想，即设计和调整催化剂（钯）嵌入植入物可以在癌细胞附近提供受控的前药转化。我们将开发包裹钯（PD）的聚合物植入物，并测试其在准2D和3D实验中前药扩散，反应和转化的功效。在同步工作中，我们打算在前药转换的硅（数学和计算）模型中开发可靠，准确的，并通过实验验证其预测。经过验证的模型将用作“计算机辅助设计平台”，以告知实验的设计以及植入物的开发。我们预见，整个框架将有助于临床医生和实践者筛选其前药策略，以确保/不可避免的特性，从而降低实验室规模的实验成本，加速发展，从而降低PD携带植入物的临床相关形式的商业化。