多功能Bio-Ag NCs负载miR-200c靶向治疗耐药乳腺癌的研究

Breast cancer is the most frequent female malignant tumor, and its drug resistance is the primary cause for therapeutic failure, for this reason, drug-loaded nano-system development is required to meet clinical demands. Our research group had previously isolated T-cell of drug resistant breast cancer nude mice as “bioreactor”, and Ag nanoclusters (Bio-Ag NCs) whose autologous biosynthesis (retransformation to donor for therapy) had good biocompatibility and tumor target, with visual potentials; literatures and experiments supported “MT deliverying Ag+ to SA” as biosynthesis mechanism; application research showed the Ag nanoclusters had the function of loading miR-200c, controlled release and tumor targetting. Therefore, the research is aimed at optimizing biosynthesis conditions according to biosynthesis mechanism of Ag nanoclusters, assessing its functions of drug load and controlled release; investigating functions of Bio-Ag NCs loading with miR-200c from four aspects, namely biocompatibility, in vivo distribution and metabolism, targeted therapy; systematically demonstrating possibility and feasibility of Bio-Ag NCs loading with miR-200c as new-type nano-drug system for the therapy of drug resistant breast cancer. We believe our research will succeed in original innovativeness, and would provide a new healthy and precise platform technology for the therapy of drug resistant breast cancer.

乳腺癌是女性最常见恶性肿瘤，耐药是其治疗失败的主要原因，需针对此开发符合临床需求的纳米载药系统。前期，本课题组分离耐药乳腺癌模型裸鼠T细胞作为“生物反应器”，自体合成（可回输供体实现治疗功能）具有良好生物相容性与肿瘤靶向性、兼具可视化潜能的银纳米簇（Bio-Ag NCs）；文献与实验支持“MT传递Ag+至SA”为其合成机制；应用研究显示该银纳米簇具备载miR-200c、控释、靶向性能。因此，本研究拟根据上述银纳米簇的合成机制优化合成条件、评估其载药与控释性能；从生物相容性、体内分布与代谢、靶向治疗三方面考察载miR-200c的Bio-Ag NCs的功能；系统论证载miR-200c的Bio-Ag NCs作为新型纳米药物系统抗耐药乳腺癌的可能性与可行性。研究如获成功，有望为耐药乳腺癌诊疗提供一种健康、精准的新型平台技术，具有源头创新性。

乳腺癌是女性最常见恶性肿瘤，耐药是其治疗失败的主要原因，需针对此开发符合临床需求的纳米载药系统。前期，本课题组分离耐药乳腺癌模型裸鼠T细胞作为“生物反应器”，自体合成（可回输供体实现治疗功能）具有良好生物相容性与肿瘤靶向性、兼具可视化潜能的银纳米簇（Bio-Ag NCs）；文献与实验支持“MT传递Ag+至SA”为其合成机制；应用研究显示该银纳米簇具备载miR-200c、控释、靶向性能。因此，本研究拟根据上述银纳米簇的合成机制优化合成条件、评估其载药与控释性能；从生物相容性、体内分布与代谢、靶向治疗三方面考察载miR-200c的Bio-Ag NCs的功能；系统论证载miR-200c的Bio-Ag NCs作为新型纳米药物系统抗耐药乳腺癌的可能性与可行性。研究如获成功，有望为耐药乳腺癌诊疗提供一种健康、精准的新型平台技术，具有源头创新性。.通过研究，本项目已圆满完成Bio-Ag NCs生物合成机制的解析并据此优化了合成条件；评估了Bio-Ag NCs对miR-200c的负载与控释能力；研究了载miR-200c的Bio-Ag NCs靶向治疗耐药乳腺癌的功能。已发表标注基金资助的SCI论文4篇。协助培养了2名硕士研究生、2名博士研究生；其中1名硕士研究生、1名博士研究生已完成论文答辩、顺利毕业；其他2名研究生已完成毕业论文的大部分实验工作，计划于2021年完成毕业论文答辩工作；目前，项目负责人分别于2019年和2020年独立招收的2名硕士研究生仍在培养中。