PD-L1-Targeted and ROS-Responsive Nanoplatform for Simultaneous Chemotherapy and Dual-Modal Imaging of Treatment Response in Triple-Negative Breast Cancer

Abstract The evaluation of treatment response in triple-negative breast cancer (TNBC) still primarily relies on tumor size and ex vivo analyses, which provide very limited information on how tumors dynamically respond during therapy. In fact, oxidative stress rapidly emerges early after drug treatment, while PD-L1 reflects an adaptive signal associated with tumors. However, these treatment-associated features are commonly assessed using static detection methods, thereby limiting longitudinal in vivo evaluation. To address this, we developed a theranostic nanoprobe named RAPP, which integrates DOX delivery, ROS-responsive near-infrared fluorescence (NIRF) imaging, and PD-L1-targeted magnetic resonance imaging (MRI). In this system, the fluorescence signal serves to report early oxidative stress in real time, while PD-L1 targeting contributes to tumor-directed MRI, enabling longitudinal assessment of both signals in a 4T1 TNBC model. During treatment, RAPP produced distinct changes in fluorescence and MR signals across different experimental groups, indicating the complementarity of these two imaging modalities in evaluating tumor response. Furthermore, DOX-loaded RAPP effectively inhibited tumor growth without exhibiting significant systemic toxicity. By integrating drug delivery with dual-modal imaging, RAPP offers a practical strategy for assessing tumor response in TNBC during treatment, rather than only after treatment completion.