Modelling of Prodrug Conversion Through Palladium Nanoparticles Encapsulated in Polymers

大多数抗癌药物都有严重的副作用，限制了它们的疗效。这些可以通过使用无害循环直到在肿瘤部位被激活的前药来减少。在这个项目中，我们提出了一个生物物理研究计划，包括一个实验和一个计算机模型，旨在开发多药癌症治疗和癌细胞化学调节的前药治疗策略。这项工作是基于推测，设计和定制催化剂（钯）嵌入植入物可以提供一个控制的前药到药物的转化癌细胞附近。我们将开发封装钯（Pd）的聚合物植入物，并在准二维和三维实验中测试其前药扩散、反应和转化的功效。在并行工作中，我们打算开发一个可靠和准确的计算机（数学和计算）模型的前药转化，并验证其预测与实验。经验证的模型将被用作“计算机辅助设计平台”，为实验设计和植入物开发提供信息。我们预见，这一整个框架将有助于临床医生和从业者筛选他们的前药策略的理想/非理想的属性，从而降低实验室规模的实验成本，加速开发，因此临床相关形式的Pd-轴承植入物的商业化。

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.