功能生物分子的原位与活体分析及其介导的癌症精准诊疗新方法

Through the utility of nanostructure assembly and biotechnology, this project focuses on the development of novel in situ and in vivo analytical methods for cancer-related functional biomolecules as the targets and cancer precision diagnostics, typing, accurate therapeutics, and therapeutic effect monitoring mediated by these molecules using cancer cells and tissues as the subjects. Starting from the new perspectives of analytical life chemistry and chemical biology, based on our previous achievements, this project will design biomimetic molecule probes with target-recognition properties, establish specific biomimetic recognition, in situ and in vivo analysis and multi-modality molecular imaging methods for cancer-related functional biomolecules, and determine the key cancer-promotion molecules and their implications in cancer diagnostics and precise typing for developing new diagnostic systems. Through the combination of molecular recognition and chemical and biological design, new near-infrared photo-sensitizers and cell apoptosis-promotion reagents will be developed to break through the current penetration depth barrier, and novel key cancer-promotion-molecule-mediated targeted therapeutic methods will be proposed. New avenues for the in situ and in vivo monitoring of multiplex specific analytes and therapeutic effect will be presented by coupling signal amplification with photo-electric signal transduction and molecular imaging technology, and the cancer incidence, development and inhibition mechanisms will be revealed with these established methods. These works will contribute significantly to the development of fields of analytical life chemistry, clinical medicine and biological sciences.

本项目将以癌症准确诊断与精准治疗为目标，以癌细胞与癌变组织为对象，以癌症相关功能生物分子为靶标，利用纳米组装与生物技术，发展功能生物分子原位与活体分析及其介导的癌症精准诊断、分型、治疗和疗效监测新方法。从精准生命分析化学和化学生物学的新角度出发，在已有工作基础上，设计靶标识别的仿生分子探针，建立特异性仿生识别及癌症相关功能生物分子的原位在体检测或多模态分子成像方法，确定癌变关键分子及其在癌症诊治与精准分型中的意义，发展诊断新体系；融合分子识别与化学和生物设计，突破现有穿透深度障碍，构建新型近红外光敏剂及细胞凋亡制剂，发展癌变关键分子介导的靶向治疗新方法；结合信号放大和光电传感与分子成像技术，提出多个特定分子同时检测方法与疗效实时活体监测的新思路，提高肿瘤分型与诊治的精准性能，并用建立的方法，揭示癌症发生、发展与抑制机制。本项目工作对于生命分析化学、临床医学和生命科学领域的发展具有积极意义。

本项目围绕功能生物分子的原位与活体分析及癌症精准诊疗展开研究，开发了多种新型仿生识别探针，建立了一系列信号放大新策略和癌症相关功能生物分子的高灵敏原位检测新方法，并用于分子分型；创建信号“开-关”新原理与成像新模式，建立了多种分子的成像方法，实现了肿瘤组织或肿瘤细胞的高效成像，并揭示了相关分子调控机制；基于上转换纳米颗粒设计近红外光激发的光动力治疗策略，提出功能分子介导的光动力治疗新原理与疗效实时原位监测新方法；构建了一系列刺激响应的纳米递药体系，并基于DNA杂交设计跨膜逻辑门原理，为癌症的准确诊断与精准治疗以及生物医学研究提供有效工具。发表标注论文92篇，其中IF大于10刊物23篇、大于5刊物80篇，国内刊物10篇。这些论文已被SCI刊物引用1505次。相关成果申请国家发明专利26件（7件已获授权），出版英文专著2部、编著2部、专章4章，获省部级一等奖、二等奖各1项、三等奖2项。项目负责人获国际与全国性学会奖各1项，在国际学术会议作主题/邀请报告25次，全国性学术会议报告27次（其中大会报告16次）。