Chunling Xie, Miao Lan, Jinmei Chen, Xiufeng Xiao
Real-time monitoring of the in situ release kinetics of nano-drug delivery systems (DDS) is crucial for enhancing the precision of cancer chemotherapy and reducing systemic toxicity. In this study, an integrated surface-enhanced Raman scattering (SERS) traceable platform (TNTs-Ag-MPBA-DOX) based on electrochemically anodized TiO2 nanotube arrays (TNTs) was developed for the real-time dynamic monitoring of pH-responsive drug release. Utilizing the highly regular three-dimensional (3D) structure and high specific surface area of TNTs, silver nanoparticles (Ag NPs) were uniformly loaded onto their inner walls and surfaces via a silver mirror reaction, constructing high-density longitudinal SERS "hot spots" distributed throughout the bulk phase to achieve enhanced SERS signals and reproducibility. 4-mercaptophenylboronic acid (4-MPBA) was introduced as a signal reporter molecule through AgS bonds, and a pH-sensitive boronic ester linkage was formed between 4-MPBA and doxorubicin (DOX) utilizing the diol structure. SERS spectroscopic analysis revealed that drug loading induced a conformational transition in the 4-MPBA spectrum, generating characteristic response peaks at 850 and 1251 cm-1; upon exposure to an acidic tumor microenvironment (pH 5.4), the dynamic cleavage of the boronic ester linkage led to DOX release and the characteristic recovery of the 4-MPBA spectral fingerprint. Experimental results demonstrated that the platform achieved a drug release rate of 90.10% within 36 h at pH 5.4, while exhibiting excellent chemical stability (86.26% signal retention after 15 days) and good biocompatibility. The "spectral switch" monitoring strategy established in this study not only provides a new tool for understanding intracellular drug release mechanisms but also offers important technical support for the real-time self-diagnosis of smart implantable medical devices.