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。可以通过使用一种前药来减少这些影响，这种前药在肿瘤部位被激活之前一直在无害地循环。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电子模型，旨在为多种药物的癌症治疗和癌细胞的化学调节开发前药物治疗策略。这项工作是基于这样一个猜想，即设计和定制催化剂(钯)植入植入物可以在癌细胞附近提供受控的前药物到药物的转化。我们将开发包裹钯(Pd)的聚合物植入物，并在准2D和3D实验中测试其前药扩散、反应和转化的效果。在并行工作中，我们打算开发一个可靠和准确的前药物转化的计算机(数学和计算)模型，并用实验验证它的预测。经过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的开发提供信息。我们预计，整个框架将帮助临床医生和从业者筛选他们的前药策略，以确定可取/不可取的特性，从而降低实验室规模实验的成本，加快开发，从而实现临床相关形式的含钯植入物的商业化。

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.