间充质干细胞膜修饰载药纳米微粒靶向杀伤口腔鳞癌机制研究

Targeted killing of oral squamous cell carcinoma (OSCC) is of great significance to reduce the side effects of chemotherapy drugs, increase the concentration of drugs in tumors, prolong the effective time and improve the killing efficiency of cancer cells. Metal organic frameworks (MOFs) are known to have a stable skeleton structure, easy to modify and biosecurity characteristics, and are suitable as drug carriers. In the previous work, we found that OSCC secretes CXCL8 in the tumor microenvironment and interacts with the surface receptor CXCR2 of dental pulp mesenchymal stem cells (DPSCs), that made them targeted homing to tumor sites. Therefore, we propose that DPSCs membrane-coated MOFs have a targeted killing effect. In this project, we will prepare pH-controlled and membrane-coated MOFs carrier, characterize the drug loading efficiency, encapsulating efficiency and controlled release ability, on the basis of MOFs constructed with organic ligand and inorganic metal center elements. We will study the effects on anti-tumor to OSCC, using cell and molecular biology techniques in vitro. The tumor-bearing nude mouse will be established for in-vivo study. We will assess the anti-tumor effects by bioimaging and histological methods, and finally clarify the targeted mechanism. The results of the study will establish a drug delivery system that targets to oral squamous cell carcinoma, and lay the foundation for clinical treatment of tumors.

靶向杀伤口腔鳞癌(OSCC)对于减少化疗药物毒副作用，增加肿瘤局部药物浓度，延长作用时间，提高癌细胞杀伤效率，具有重要意义。已知金属有机框架(MOFs)拥有稳定骨架结构，连续可调多孔性，易于修饰和良好生物安全性等特点，适合作为药物载体；OSCC在肿瘤微环境中分泌CXCL8，其与牙髓间充质干细胞(DPSCs)表面受体CXCR2相互作用，趋化DPSCs靶向归巢。因此本项目研究提出间充质干细胞膜包覆载药金属有机框架具有靶向杀伤口腔鳞癌作用的科学假设。基于前期工作基础，通过配位竞争诱导聚方法制备pH控释DPSCs膜包覆的载药MOFs，表征其载药率、包封率及控制释放能力；采用细胞生物学和分子生物学手段研究其对OSCC的抑制作用；建立裸鼠荷瘤模型，通过生物成像和组织学方法评价其靶向抗癌效果；阐明其对OSCC靶向性的作用机理。研究结果将建立一种新型靶向杀伤口腔鳞癌的药物传递体系，为肿瘤临床治疗奠定基础。

靶向杀伤口腔鳞癌(OSCC)对于减少化疗药物毒副作用，增加肿瘤局部药物浓度，延长作用时间，提高癌细胞杀伤效率，具有重要意义。已知金属有机框架(MOFs)拥有稳定骨架结构，连续可调多孔性，易于修饰和良好生物安全性等特点，适合作为药物载体；OSCC在肿瘤微环境中分泌CXCL8，其与牙髓间充质干细胞(DPSCs)表面受体CXCR2相互作用，趋化DPSCs靶向归巢。因此本项目研究提出间充质干细胞膜包被载药金属有机框架具有靶向杀伤口腔鳞癌作用的科学假设。基于前期工作基础，通过配位竞争诱导聚方法制备pH控释DPSCs膜包覆的载药MOFs，表征其载药率、包封率及控制释放能力；采用细胞生物学和分子生物学手段研究其对OSCC的抑制作用；建立裸鼠荷瘤模型，通过生物成像和组织学方法评价其靶向抗癌效果；阐明其对OSCC靶向性的作用机理。研究结果将建立一种新型靶向杀伤口腔鳞癌的药物投递体系，为肿瘤临床治疗奠定基础。