基于聚多巴胺-二甲双胍的纳米药物用于核素／光声成像引导下肿瘤放化疗协同治疗研究

The combination of tumor radiotherapy and chemotherapy in the clinical treatment is widely used. However, how to overcome the resistance of radiotherapy and chemotherapy and improve the sensitivity of tumor cells to radiotherapy and chemotherapy, is a major challenge in the radiotherapy and chemotherapy. Metformin, as a clinical recommendation for hypoglycemic agent, has been found to inhibit the tumor and enhance the sensitivity of radiotherapy and chemotherapy in recent years. Herein, we plan to design and synthesize a biocompatible polydopamine nanoparticles, and modify its surface with polyethylene glycol. Then 131I with radiotherapy function is labeled on the nanoparticles, followed by loading metformin and chemotherapeutic drug cisplatin into nanoparticles. Finally a combination of radiotherapy and chemotherapy integrated multi-functional nano-drug delivery system is constructed. With the characteristics of photoacoustic imaging contrast agent of polydopamine, we employ radionuclide imaging and photoacoustic imaging to achieve dual-mode imaging guided combination of radiotherapy and chemotherapy by polydopamine nano-drug and efficacy monitoring. Furthermore, we try to reveal its molecular mechanisms of sensitizing chemo-radiotherapy and anti-tumor effect by nanodrug, and to provide new monitoring methods and therapeutic tools for tumor radiotherapy and chemotherapy.

肿瘤的放化疗协同治疗在临床中被广泛应用。然而，如何克服放化疗抗拒，提高肿瘤细胞对放化疗的敏感性，是肿瘤放化疗协同治疗中面临的重大挑战。二甲双胍作为临床推荐降糖药，近年来发现具有抑制肿瘤、增强放化疗敏感性等作用。本项目拟设计合成具有生物相容性的聚多巴胺纳米颗粒，并对其表面进行聚乙二醇修饰，将具有放射治疗功能的碘131标记到纳米颗粒上，再将二甲双胍和化疗药物顺铂装载到纳米颗粒上，构建一种兼具放疗和化疗一体化的多功能纳米载药系统，同时利用聚多巴胺可作为光声成像造影剂的特性，采用放射性核素成像和光声成像实现双模态成像指导下的聚多巴胺纳米药物对肿瘤的放化疗协同治疗及疗效监测，并进一步揭示其增敏放化疗和抗肿瘤作用的分子机制，为肿瘤的放化疗协同治疗提供新的监测手段和治疗工具。

肿瘤的放化疗协同治疗在临床中被广泛应用。然而，如何克服放化疗抗拒，提高肿瘤细胞对放化疗的敏感性，是肿瘤放化疗协同治疗中面临的重大挑战。二甲双胍作为临床推荐降糖药，近年来发现具有抑制肿瘤、增强放化疗敏感性等作用。本项目成功设计合成了具有生物相容性的聚多巴胺纳米颗粒，并对其表面进行聚乙二醇修饰，将具有放射治疗功能的碘131标记到纳米颗粒上，再将二甲双胍和化疗药物顺铂装载到纳米颗粒上，成功构建了一种兼具放疗和化疗一体化的多功能纳米载药系统，同时利用聚多巴胺可作为光声成像造影剂的特性，采用放射性核素成像和光声成像实现了双模态成像指导下的聚多巴胺纳米药物对肿瘤的放化疗协同治疗及疗效监测，并进一步揭示了其增敏放化疗和抗肿瘤作用的分子机制，为肿瘤的放化疗协同治疗提供新的监测手段和治疗工具。在该项目资助下，项目负责人以通讯作者在Nucleic Acids Research (IF 16.9), Molecular Therapy (IF 11.4), Cell death & Disease (IF 8.4), Cancer letters (IF 8.6), Analytical Chemistry (IF 6.98) 等国际学术期刊以通讯作者发表论文18篇（均标注此基金号），申请发明专利 6 项，其中授权4项。