蛋白多肽类药物（PPD）的体内定量分析是其研发评价的重要环节。液质联用作为体内药物分析的主要方法，直接用于体内PPD分析时存在样品处理困难、灵敏度低等问题；常用的免疫学分析方法也存在线性范围窄、重现性差等缺陷。为解决上述问题，本项目提出基于“适配体识别”和“刺激响应介孔材料信号转导”的PPD定量分析新方法。即采用“磁响应探针”和“刺激响应微纳米囊探针”表面的适配体分别特异地识别生物样品中同一PPD，形成复合物，外加磁场使该复合物分离纯化，通过外界刺激触发闭孔剂使孔解锁，以释放微纳米囊中负载的“信号分子”代替目标PPD进行检测，完成检测目标转换和信号转导。该方法可以专属地分离PPD，同时对检测信号的数量和响应进行放大，从而实现生物样品中PPD的高灵敏度检测。此外，选择具有荧光响应的“信号分子”还可达到“可视化”检测的效果。本研究将为PPD体内定量测定及研发提供新方法和新思路。

Biopharmaceutical analysis has become an important part of the development and evaluation of protein and polypeptide drugs (PPD). LC-MS is the main method to determine drugs in vivo. However, the determination of PPD in biological samples by LC-MS directly exists some problems, such as difficulties in sample pretreatment process and low sensitivity. The methods currently used for determination of PPD in vivo,such as the immunosorbent assay methods also present some disadvantages, like narrow linear range, bad precision and low sensitivity. In view of the above problems, this project intends to combine “aptamer-recognition” and “signal transduction of stimulus-responsive mesopores materials” to develop a novel method for quantification of PPD. The aptamers on the surface of the “magnetic nanoparticles probes” and “stimulus-responsive Micro-/Nanocontainers probes” can recognize specifically the same PPD in the biological samples and form complexes. Then the complexes can be purified by magnetic field. Lastly, the pore-capping units should be unlocked with external triggers, allowing the controlled release of the signal molecules from the stimulus-responsive Micro-/Nanocontainers probes. The “signal molecules” can be detected instead of the targeted PPD, which can achieve the conversion of the target to detect and the transduction of signal simultaneously. Thus the method could achieve high sensitivity, as the PPDs can be enriched and extracted specifically from the biological samples and the detectable amounts of the targeted PPD would be amplified with more signal molecules. In addition, the “signal molecules” with fluorophore can also achieve the “visual” detection. This study will provide a novel method for the quantification of PPD in biological samples.