Cui Jia, Zhang Taixing, Wang Fei, Feng Lingzi, Deng Guangjun, Wu Ting, Yin Le, Hu Yong
MOE Key Laboratory of High Performance Polymer Materials and Technology, College of Engineering and Applied Sciences, Nanjing University, Nanjing 210023, China.
Tongzhou Renming Hospital, 999 Jianshe Road, Jinsha Town, Tongzhou District, Nantong 226030, China.
Nanomaterials (Basel). 2024 Oct 18;14(20):1673. doi: 10.3390/nano14201673.
Autophagy leads to cellular tolerance of the therapeutic pressure of chemotherapeutic drugs, resulting in treatment resistance. Therefore, the effective monitoring of the autophagy status of tumors in vivo and the regulating of the autophagy level are crucial for improving the efficacy of chemotherapy. In this work, we grafted nitroxide radicals onto the surface of iron oxide nanoparticles (FeO NPs) using dendrimer polymers, yielding FeO-NO· NPs that are responsive to reactive oxygen species (ROS) and possess enhanced T1 and T2 signal capabilities in a magnetic resonance imaging (MRI) measurement. The ROS in tumor cells generated by autophagy quenches the nitroxide radicals, thereby weakening the T1 signal. In contrast, FeO NPs are unaffected by intracellular ROS, leading to a stable T2 signal. By comparing the intensity ratio of T1 to T2 in FeO-NO· NPs, we can evaluate the in vivo autophagy status within tumors in real time. It also revealed that FeO-NO· NPs loaded with doxorubicin (Dox) and combining the autophagy inhibitor exhibited high antitumor activity in cells and tumor-bearing mice. This system, which combines real-time monitoring of tumor cell autophagy with the delivery of chemotherapeutic drugs, provides an innovative and effective strategy for tumor treatment with potential clinical application prospects.
自噬导致细胞对化疗药物治疗压力产生耐受性，从而导致治疗抵抗。因此，有效监测体内肿瘤的自噬状态并调节自噬水平对于提高化疗疗效至关重要。在这项工作中，我们使用树枝状聚合物将氮氧自由基接枝到氧化铁纳米颗粒（FeO NPs）表面，得到对活性氧（ROS）有响应且在磁共振成像（MRI）测量中具有增强的T1和T2信号能力的FeO-NO· NPs。自噬产生的肿瘤细胞中的ROS淬灭氮氧自由基，从而减弱T1信号。相比之下，FeO NPs不受细胞内ROS的影响，导致T2信号稳定。通过比较FeO-NO· NPs中T1与T2的强度比，我们可以实时评估肿瘤内的体内自噬状态。研究还表明，负载阿霉素（Dox）并结合自噬抑制剂的FeO-NO· NPs在细胞和荷瘤小鼠中表现出高抗肿瘤活性。该系统将肿瘤细胞自噬的实时监测与化疗药物递送相结合，为肿瘤治疗提供了一种具有潜在临床应用前景的创新有效策略。
