Chen Qingjie, Yang Jianbo, Yang Mei, Luo Zhaoxia, Lei Yangyang, Zhang Qing
Department of Nuclear Medicine, The First Affiliated Hospital of Nanchang University, No. 17, Yongwai Zhengjie, Donghu District, Nanchang, 330006, Jiangxi Province, China.
Apoptosis. 2025 Jul 23. doi: 10.1007/s10495-025-02141-w.
Sepsis-induced acute kidney injury (AKI) is a critical condition characterized by high mortality and limited early diagnostic tools. This study presents the development of a novel multimodal nanoprobe, Ga/99mTc@LTH-SPIONs, for targeted detection and monitoring of sepsis-induced AKI. By combining PET/SPECT imaging capabilities of radiolabeled isotopes (Ga and 99mTc) with the anatomical resolution of superparamagnetic iron oxide nanoparticles (SPIONs) for MRI, the nanoprobe facilitates precise and non-invasive imaging. Surface modification with the LTH peptide, which specifically targets Kidney Injury Molecule-1 (Kim-1), enhances the nanoprobe's diagnostic specificity. Extensive in vitro and in vivo evaluations revealed low cytotoxicity, excellent biocompatibility, and effective renal targeting, with metabolites predominantly cleared through urine. In a sepsis AKI mouse model, the nanoprobe provided sensitive and specific imaging, enabling early detection of kidney injury. This study underscores the potential of Kim-1-targeted nanoprobes as a powerful tool for elucidating cellular injury mechanisms and monitoring therapeutic interventions in AKI.
脓毒症诱导的急性肾损伤（AKI）是一种危急病症，其特征是死亡率高且早期诊断工具有限。本研究展示了一种新型多模态纳米探针Ga/99mTc@LTH-SPIONs的研发，用于脓毒症诱导的AKI的靶向检测和监测。通过将放射性标记同位素（Ga和99mTc）的PET/SPECT成像能力与用于MRI的超顺磁性氧化铁纳米颗粒（SPIONs）的解剖分辨率相结合，该纳米探针有助于进行精确的非侵入性成像。用特异性靶向肾损伤分子-1（Kim-1）的LTH肽进行表面修饰，提高了纳米探针的诊断特异性。广泛的体外和体内评估显示其细胞毒性低、生物相容性优异且具有有效的肾脏靶向性，代谢产物主要通过尿液清除。在脓毒症AKI小鼠模型中，该纳米探针提供了灵敏且特异的成像，能够早期检测肾脏损伤。本研究强调了靶向Kim-1的纳米探针作为阐明AKI细胞损伤机制和监测治疗干预的有力工具的潜力。
