基于核酸适配体—超小钯纳米片多功能诊疗平台的构建及其在胰腺癌早期诊疗中的应用研究

Pancreatic adenocarcinoma is one of the most fatal cancers, and its therapeutic effect and survival rate are closely related to the diagnosis and treatment time. Therefore, the development of new theranostic probes with high sensitivity for early diagnosis and treatment of pancreatic adenocarcinoma has become the key factor for improving survival rate of patients with pancreatic cancer. In recent years, the application of aptamer-nanomaterials based multifunctional theranostic probes in the early diagnosis and treatment of cancer has attracted much attention. However, the long-term biosafety of nanomaterials that applied in these theranostic probes has been an issue of concern. Moreover, the diagnosis and treatment of tumor cannot be achieved at the same time due to the single function of traditional probes. To solve the problems mentioned above, this project intended to construct a theranostic platform based on aptamer with high binding affinity and specificity to pancreatic ductal adenocarcinoma and ultra-small Pd nanosheets with renal clearance property for the early diagnosis and treatment of pancreatic carcinoma. Through the modification of near infrared fluorescent dyes and radiolabelling, a multifunctional platform with fluorescence imaging, photoacoustic imaging and SPECT/CT imaging and combined cancer therapy based on photothermal therapy and radiotherapy were successfully constructed, thus providing an effective way for the early diagnosis and treatment of pancreatic cancer.

胰腺癌作为恶性肿瘤的典型代表，其治疗效果和存活率与诊疗时机密切相关。因此，发展新型高灵敏胰腺癌早期诊疗探针，实现胰腺癌的早期诊断和治疗，成为提高胰腺癌患者存活率的关键因素。近年来，基于核酸适配体—纳米材料的多功能探针在肿瘤早期诊疗中的应用得到了广泛的关注，但目前诊疗探针所用的纳米材料在生物应用过程中的安全性问题逐渐引起大家的关注。而传统诊疗探针功能单一，主要体现在成像模式单一和无法同时实现肿瘤的诊断和治疗。因此，本项目拟将具有特异性识别胰腺导管腺癌的核酸适体与超小可经肾代谢出体外的超小纳米材料结合，通过修饰近红外荧光染料和放射性元素，构建具有集荧光成像、光声成像及SPECT/CT成像和光热+放疗联合治疗的靶向早期胰腺癌的诊疗平台，为胰腺癌的早期诊疗提供新的技术支持。

纳米技术的发展为恶性肿瘤诊疗提供了新的技术支持，新型癌症早期纳米诊疗探针的研发成为提高癌症患者存活率的关键。但目前纳米诊疗体系仍然存在两方面问题：诊疗体系所用的纳米材料在生物应用过程中的安全性问题未能引起足够的重视；传统诊疗体系功能单一，主要体现在成像模式单一和无法同时实现肿瘤的诊断和治疗。本项目通过系统研究超薄二维纳米材料的生物学行为，基于超小二维钯基纳米片构建了放射性核素标记多功能诊疗平台用于肿瘤多模态成像与联合治疗。针对肿瘤发展过程中微环境的乏氧、偏酸性等特点，进一步将“微环境响应”策略应用到功能探针的构建中，发展了系列生物安全性高、肿瘤富集能力强、成像模式多样化和治疗效率高的纳米诊疗平台。同时，针对疾病标志物早期检测发展了系列新型荧光功能材料和生物传感新方法用于高灵敏生物分子检测。