Modelling the biophysical barriers to drug delivery in cancer

为了治疗癌症等疾病而注射到人体心血管系统的药物，在到达患病区域之前会遇到许多生物物理障碍。其中包括内皮屏障——血管系统的物理壁，药物必须首先有效地通过。一旦越过血管系统，药物就会遇到机械刚性、缺氧的病变基质，这可能会对有效的药物治疗提出另一个物理和化学障碍。这些生物物理障碍阻碍并降低了药物治疗的有效性，导致治疗失败和疾病复发。然而，它们存在于体内，实验室的药物筛选并没有考虑到这些关键的物理障碍，这些物理障碍导致药物在实验室有效，但一旦进入临床就失败了。该项目将开发微流体、器官芯片技术，以模拟化疗药物在癌症治疗中遇到的生物物理障碍。特别是，设备将被设计和工程来培养人体微血管，以解开血管-药物的相互作用。此外，这些下一代模型将用于研究新的治疗方法，如微泡，作为治疗癌症的传统方法的替代，改进的药物输送途径。

Drugs that are injected into cardio-vasculature system the body in order to treat diseases such as cancer, encounter a number of biophysical barriers before ever reaching the diseased area. These include the endothelial barrier - the physical walls of the vasculature system, through which a drug must first pass effectively. Once beyond the vasculature system, the drugs encounter a mechanically rigid, oxygen depleted diseased matrix that can present another physical and chemical barrier to effective drug treatment. These biophysical barriers block and reduce the effectiveness of drug treatment, leading to treatment failure and disease re-occurrence. Yet their presence in the body, drug screening in the laboratory does not take into account these critical physical barriers leading to drugs that are effective in the lab, but fail once in clinic. This project will develop microfluidic, organ-on-chip technology to model the biophysical barriers encountered by chemotherapeutics in cancer treatment. In particular, devices will be designed and engineered to culture human microvasculature in order to unravel vasculature - drug interactions. In addition, these next-generation models will be used to investigate new therapeutics, such as microbubbles, as an alternative, improved route to drug delivery compared to conventional methods in treating cancer.