本课题拟设计上转换荧光纳米粒子（UCNP）-内标化表面增强拉曼散射（SERS）二元纳米光学探针作为标记和传感材料，用于构建纳米药物，借助荧光和拉曼双模成像技术实现其体内行为研究。该二元探针为UCNP和SERS探针通过互补DNA单链偶联形成的纳米二聚体。进一步在二聚体表面生成载药材料纳米层，并装载抗肿瘤药物阿霉素（DOX）。利用探针中内标化的SERS “稳定信号”，以及DOX从载药层解离引发、基于“荧光共振能量转移”和“壳层隔绝纳米粒子增强拉曼光谱”原理测定的荧光/SERS二元“可变信号”，实现在载药纳米药物、游离药物和释药后载体三个形态的同时、动态监测。该方法不但突破了传统成像技术中载体定位和药物释放研究过程割裂的难题，而且具有深层检测、灵敏准确、实时动态的优点。有助于在细胞和活体水平研究纳米药物的摄入、富集、释药及代谢的动态过程，为揭示其药理药效机制、促进纳米剂型研发提供重要技术。

In this plan, we aim to synthesize upconversion fluorescent nanoparticle (UCNP)-internal standard surface enhanced Raman scattering (SERS) bimodal nanoprobes for the tracking and drug release study of nanomedicine in vivo via fluorescence and Raman imaging systems. In this bimodal nanoprobe, UCNP and SERS tag are linked via complementary DNA hybridization, forming a nano-dimer. Furthermore, a thin layer of drug loading material is coated on the surface of nano-dimer, followed by the adsorption of anti-tumor drug doxorubicin (DOX). Taking advantages of the stable signal from internal standard SERS tag, and the DOX release-triggered variable fluorescence/SERS signals originating from fluorescence resonance energy transfer (FRET) and shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) principle, the three forms of nanomedicine, i.e., drug containing nanomedicine, released drug molecule, and nanocarrier, can be simultaneously monitored. This method overcomes the problem of traditional optical imaging way, in which the issues of nanomedicine locating and drug release are studied separately. Furthermore, it has the feature of low background, high detection sensitivity and accuracy, and can be applied in a real-time and dynamic way. Our investigation will be helpful for revealing the uptake, distribution and final fate of nanomaterials in living cells and small animals, and promote research and development of novel namomedicine with high treatment efficiency.