An injectable hydrogel for co-delivery of immunotherapy and chemotherapy drugs

将药物直接递送到肿瘤部位是有吸引力的，因为它降低了全身毒性并允许在肿瘤部位递送更高剂量的药物。该项目旨在开发一种药物洗脱剪切稀化材料，能够使用微创手术将多种药物输送到肿瘤。我们最近开发了一种由明胶和合成纳米粘土组成的纳米复合水凝胶，该纳米复合水凝胶具有生物可降解性和生物相容性。所提出的水凝胶在暴露于高剪切应力时经历可逆的粘度降低;因此，它可以以最小的所需力通过医用导管或手术针注射。为了提供这种材料，我们将利用我们正在申请专利的手持式注射装置，该装置能够精确地提供水凝胶。在这个项目中，我们将与麻省理工学院的合作伙伴合作，将免疫治疗剂加载到水凝胶上，并确定最佳药物剂量和释放曲线，以最大限度地提高药物的治疗效果。为了实现这一目标，第四年的博士学位。学生将被派往我们国际合作者的实验室，以获得分子细胞生物工程技术的实践经验，并将其用于科学级的应用。该项目帮助学员发展研究技能，如定量实验测定，患者来源的细胞培养方法和癌症免疫治疗，这是实现本提案目标所必需的。

Delivering drugs directly to the site of a tumor is attractive because it reduces systemic toxicities and allows for delivering higher doses of drugs at the tumor site. This project aims to develop a drug-eluting shear-thinning material capable of delivering multiple drugs to a tumor using minimally-invasive surgeries. We have recently developed a nanocomposite hydrogel composed of gelatin and a synthetic nanoclay that is biodegradable and biocompatible. The proposed hydrogel undergoes a reversible reduction in viscosity upon exposure to high shear stresses; thereby, it can be injected through medical catheters or surgical needles with a minimum required force. To deliver this material, we will utilize our patent-pending hand-held injection device that enables the precise delivery of hydrogels. In this project, we will collaborate with our partner at MIT to load immunotherapy agents onto the hydrogel and determine optimum drug dosages and release profiles that maximize the therapeutic outcomes of the drugs. To achieve this goal, a fourth-year Ph.D. student will be sent to our international collaborator's lab to gain hands-on experience in molecular cell bioengineering techniques and to use them in a scientific-class application. This project helps the trainee develop research skills such as quantitative experimental assays, patient-derived cell culture methodology, and cancer immunotherapy, which are required to achieve the goals of this proposal.