Huang Xueqin, Sheng Bingbing, Tian Hemi, Chen Qiuxia, Yang Yingqi, Bui Brian, Pi Jiang, Cai Huaihong, Chen Shanze, Zhang Jianglin, Chen Wei, Zhou Haibo, Sun Pinghua
The Second Clinical Medical College (Shenzhen People's Hospital), College of Pharmacy, Jinan University, Guangzhou, 510632, China.
Department of Physics, the University of Texas at Arlington, Arlington, TX 76019, USA.
Acta Pharm Sin B. 2023 Mar;13(3):1303-1317. doi: 10.1016/j.apsb.2022.08.024. Epub 2022 Sep 5.
and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy. In this study, a novel pH-responsive nanosystem is proposed for real-time monitoring of drug release and chemo-phototherapy by surface-enhanced Raman spectroscopy (SERS). The FeO@Au@Ag nanoparticles (NPs) deposited graphene oxide (GO) nanocomposites with a high SERS activity and stability are synthesized and labeled with a Raman reporter 4-mercaptophenylboronic acid (4-MPBA) to form SERS probes (GO-FeO@Au@Ag-MPBA). Furthermore, doxorubicin (DOX) is attached to SERS probes through a pH-responsive linker boronic ester (GO-FeO@Au@Ag-MPBA-DOX), accompanying the 4-MPBA signal change in SERS. After the entry into tumor, the breakage of boronic ester in the acidic environment gives rise to the release of DOX and the recovery of 4-MPBA SERS signal. Thus, the DOX dynamic release can be monitored by the real-time changes of 4-MPBA SERS spectra. Additionally, the strong T magnetic resonance (MR) signal and NIR photothermal transduction efficiency of the nanocomposites make it available for MR imaging and photothermal therapy (PTT). Altogether, this GO-FeO@Au@Ag-MPBA-DOX can simultaneously fulfill the synergistic combination of cancer cell targeting, pH-sensitive drug release, SERS-traceable detection and MR imaging, endowing it great potential for SERS/MR imaging-guided efficient chemo-phototherapy on cancer treatment.
响应性药物释放的实时监测对于化疗药效学评估至关重要。在本研究中,提出了一种新型pH响应纳米系统,用于通过表面增强拉曼光谱(SERS)对药物释放和化学光疗进行实时监测。合成了具有高SERS活性和稳定性的FeO@Au@Ag纳米颗粒(NPs)沉积氧化石墨烯(GO)纳米复合材料,并用拉曼报告分子4-巯基苯硼酸(4-MPBA)进行标记,以形成SERS探针(GO-FeO@Au@Ag-MPBA)。此外,阿霉素(DOX)通过pH响应性连接体硼酸酯连接到SERS探针上(GO-FeO@Au@Ag-MPBA-DOX),伴随SERS中4-MPBA信号的变化。进入肿瘤后,硼酸酯在酸性环境中断裂,导致DOX释放和4-MPBA SERS信号恢复。因此,DOX的动态释放可以通过4-MPBA SERS光谱的实时变化进行监测。此外,纳米复合材料的强T磁共振(MR)信号和近红外光热转换效率使其可用于MR成像和光热治疗(PTT)。总之,这种GO-FeO@Au@Ag-MPBA-DOX可以同时实现癌细胞靶向、pH敏感药物释放、SERS可追踪检测和MR成像的协同组合,赋予其在SERS/MR成像引导下高效化疗光疗癌症治疗方面的巨大潜力。