由活性氧（ROS）响应药物递送系统介导的化疗可以潜在地减轻化疗药物的毒副作用并显着提高其治疗效果。然而，在肿瘤部位实现精确的靶向药物递送和实时控制 ROS 响应药物的释放仍然是一个艰巨的挑战。因此，本研究旨在描述一种具有特定肿瘤靶向能力的ROS响应药物递送系统，以减轻化疗引起的毒性，同时在荧光（FL）和磁共振（MR）双模成像指导下增强治疗效果。吲哚菁绿（ICG）采用双重乳化法将阿霉素（DOX）前药pB-DOX和超顺磁性氧化铁（SPIO，Fe3O4）封装在聚乳酸-乙醇酸（PLGA）中，制备ICG/ pB-DOX/ Fe3O4/ PLGA纳米粒（ IBFP NP）。通过碳二亚胺方法用乳房珠蛋白抗体（mAbs）对IBFP NPs的表面进行功能化，构建乳腺癌靶向mAbs/IBFP NPs（MIBFP NPs）。此后，在体外和体内评估了 MIBFP NP 的 FL 和 MR 双峰成像能力。最后，对基于MIBFP NPs的联合光动力治疗（PDT）和化疗疗效评价进行了研究。多功能MIBFP NPs对乳腺癌表现出显着的靶向疗效。 FL 和 MR 双模成像清楚地显示了靶向 MIBFP NP 的体内分布。在近红外激光照射下，负载 ICG 的 MIBFP NP 有效产生用于 PDT 的 ROS，从而实现精确的肿瘤消融。同时，它通过裂解其敏感部分触发pB-DOX的激活，从而恢复DOX活性并实现ROS响应的靶向化疗。此外，MIBFP NPs将PDT和化疗结合起来，在双模态成像引导下提高肿瘤消融的效率。MIBFP NPs构成了一种新型的双模态成像引导的靶向乳腺癌给药系统，为乳腺癌靶向治疗提供了精确、可控的联合治疗选择。 © 2024 江等人。

Chemotherapy mediated by Reactive oxygen species (ROS)-responsive drug delivery systems can potentially mitigate the toxic side effects of chemotherapeutic drugs and significantly enhance their therapeutic efficacy. However, achieving precise targeted drug delivery and real-time control of ROS-responsive drug release at tumor sites remains a formidable challenge. Therefore, this study aimed to describe a ROS-responsive drug delivery system with specific tumor targeting capabilities for mitigating chemotherapy-induced toxicity while enhancing therapeutic efficacy under guidance of Fluorescence (FL) and Magnetic resonance (MR) bimodal imaging.Indocyanine green (ICG), Doxorubicin (DOX) prodrug pB-DOX and Superparamagnetic iron oxide (SPIO, Fe3O4) were encapsulated in poly(lactic-co-glycolic acid) (PLGA) by double emulsification method to prepare ICG/ pB-DOX/ Fe3O4/ PLGA nanoparticles (IBFP NPs). The surface of IBFP NPs was functionalized with mammaglobin antibodies (mAbs) by carbodiimide method to construct the breast cancer-targeting mAbs/ IBFP NPs (MIBFP NPs). Thereafter, FL and MR bimodal imaging ability of MIBFP NPs was evaluated in vitro and in vivo. Finally, the combined photodynamic therapy (PDT) and chemotherapy efficacy evaluation based on MIBFP NPs was studied.The multifunctional MIBFP NPs exhibited significant targeting efficacy for breast cancer. FL and MR bimodal imaging clearly displayed the distribution of the targeting MIBFP NPs in vivo. Upon near-infrared laser irradiation, the MIBFP NPs loaded with ICG effectively generated ROS for PDT, enabling precise tumor ablation. Simultaneously, it triggered activation of the pB-DOX by cleaving its sensitive moiety, thereby restoring DOX activity and achieving ROS-responsive targeted chemotherapy. Furthermore, the MIBFP NPs combined PDT and chemotherapy to enhance the efficiency of tumor ablation under guidance of bimodal imaging.MIBFP NPs constitute a novel dual-modality imaging-guided drug delivery system for targeted breast cancer therapy and offer precise and controlled combined treatment options.© 2024 Jiang et al.