实时荧光成像的近红外光控水凝胶载药体系的构建研究

The ability to control and monitor in vivo bio-macromolecular release with high efficiency is essential for precise target treatment. Photo-responsive drug delivery systems based on hydrogels, with fluorescence imaging, has immense potential in such fields due to its ability to allow remote and precise control of drug release over both timing and dosage. However, common fluorescence imaging techniques are often limited in both sensitivity and resolution by background fluorophore emissions, thus making them incapable of accurately reflecting moments of drug release. Therefore, developing smart-systems in which the fluorescence properties for imaging purposes are automatically triggered by the degradation of hydrogel during drug-cargo delivery would be a significant step forward in the field of in vivo drug-delivery. This project focuses on designing such a hydrogel system that can be activated with NIR signals (Near Infrared) for real-time monitored and controlled drug release as mentioned above. This can be achieved by functionalizing poly(ethylene glycol) (PEG) precursors with photoactivatable fluorescent probes, which does not exhibit fluorescent properties in gel-state and loading upconverting nanoparticles (UCNPs) while polymerization. The designed system combining the ability of sensing, drug-release and real-time monitoring would shed light on drug release processes in vivo and provide reference for future development of other multi-purpose smart systems in various fields.

有效控制并监测生物大分子药物在体内缓慢释放是临床精准治疗的关键。光响应水凝胶载药体系与荧光成像技术的结合，能够实现远程、精确、即时控制药物释放的时间和剂量。然而，常规荧光成像的分辨率和灵敏度受限于背景荧光的干扰，并不能准确反映药物释放过程的瞬时变化。因此，设计自身荧光随光控降解实时开启的水凝胶载药体系，对于研究药物在体内可控释放有着重要意义。本项目拟通过近红外荧光素（Aza-BODIPY）和邻硝基苄基类光扳机组成光激活荧光探针，联接聚乙二醇水凝胶交联网络，并在交联时加入上转换纳米颗粒（UCNP），探索制备降解过程实时成像的新型近红外光响应的水凝胶载药系统。该水凝胶不仅可以光控降解，释放生物大分子，而且在降解时会发生从‘无’到‘有’的近红外荧光变化，从而实时显示生物大分子体内释放的动态过程，建立集传感、执行和反馈于一体的智能光敏水凝胶载药体系。为可控药物缓释材料的开发提供新的思路。

如何有效负载和监测药物分子在体内缓慢释放是临床精准治疗的关键。光敏水凝胶载药体系与荧光成像技术的结合，能够实现药物的有效负载与监测,达到更精准的治疗效果。本项目设计并成功开发了降解实时监测的光敏水凝胶载药体系。通过将近红外荧光探针（Aza-BODIPY）和邻硝基苄基类光敏分子引入水凝胶交联网络，成功制备了具有实时近红外荧光成像功能的光敏水凝胶载药体系。并将诊疗一体药物分子装载入该水凝胶体系，成功在小鼠荷瘤模型上验证了其良好的肿瘤治疗效果，并揭示了其抑制肿瘤转移的生物学机制，为可控药物缓释材料的开发提供新的思路。

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