Designing Peptide hydrogels as vehicles for targeted and localised in-vivo therapeutics delivery

生命科学和生物医学领域的关键工程挑战之一是设计和制造用于3D细胞培养、组织工程和细胞/药物输送的定制水凝胶。无论是在体外用于研究细胞行为、毒性测试或组织工程，还是在体内用于细胞和/或药物的输送，或者用于促进受损组织的再生，这些高度水合的软材料都支撑着生物技术和生物医学行业的一个庞大且不断增长的部门。在这种背景下，开发体内可注射和生物相容的水凝胶用于靶向和局部输送治疗药物，无论是小药物、大生物化合物，甚至是细胞，一直是工程师、生物学家和临床医生重要工作的重点。通过这个项目，我们的目标是通过Saiani教授、Miller教授和Finegan博士的跨学科合作，开发新型可注射多肽水凝胶系统，用于实体瘤治疗中的局部治疗。该项目将包括三个主要阶段。首先，选定的治疗化合物将包括众所周知的抗癌药物阿霉素，将与水凝胶一起配制，并对其释放动力学进行研究，目的是设计将治疗化合物保留在水凝胶中以允许长期释放的系统。随后，开发的新配方将在癌细胞上进行测试，以确保水凝胶不会导致治疗化合物失活或降解，并且水凝胶分子构建块不会干扰治疗作用途径。最后，最有希望的配方将使用小动物癌症模型进行测试，以了解开发的新型水凝胶递送载体对实体肿瘤进化和消退的影响。

One of the key engineering challenges in the life-science and biomedical sectors is the design and manufacturing of bespoke hydrogels for 3D cell culture, tissue engineering and cell/drug delivery. These soft highly hydrated materials underpin a large and growing sector of biotech and biomed industries whether they are used in-vitro for the study of cell behaviour, toxicity testing or tissue engineering, or in-vivo for the delivery of cells and/or drugs or to promote regeneration of damaged tissues. In this context the development of in-vivo injectable and biocompatible hydrogels for the targeted and localised delivery of therapeutics whether small drugs, large biological compounds or even cells, has been the focus of significant work from engineers, biologists, and clinicians alike. Through this project we aim to develop through an interdisciplinary collaboration involving Prof Saiani Prof Miller and Dr Finegan groups novel injectable peptide-based hydrogel systems for localised therapeutics delivery in the context of solid cancer tumour treatment.The project will involve three main stages. First the selected therapeutical compounds, which will include Doxorubicin a well know cancer drug, will be formulated with the hydrogels and their release kinetic investigated with the aim to design systems that retain the therapeutical compound within the hydrogel allowing for prolonged release. Subsequently the novel formulations developed will be tested on cancer cells to ensure that the hydrogels do not result in the therapeutic compounds being de-activated or degraded and that the hydrogel molecular building blocks do not interfere with the therapeutic action pathway. Finally, the most promising formulations will be test using a small animal cancer model to understand the effect the novel hydrogel-based delivery vehicles developed on solid tumour evolution and regression.