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用于体内成像和治疗监测的骨靶向白蛋白纳米医学

Bone-Seeking Albumin-Nanomedicine for In Vivo Imaging and Therapeutic Monitoring.

机构信息

The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou 215004, P. R. China.

State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, 199 Renai Road, Suzhou Industrial Park, Suzhou 215123, P. R. China.

出版信息

ACS Biomater Sci Eng. 2020 Jan 13;6(1):647-653. doi: 10.1021/acsbiomaterials.9b01195. Epub 2019 Dec 30.

Abstract

Malignant osteolysis associated with irreversible primary bone tumors and bone metastases remains a clinically urgent problem. Exploiting the imaging and therapy function of flexible nanomedicine can provide an alternative for therapeutic navigation and monitoring of malignant osteolysis. Here, we report the development of albumin-based gadolinium oxide nanoparticles loaded with doxorubicin and conjugated with bone-seeking alendronate for targeted delivery and therapeutic monitoring. Compared with nontargeted nanomedicine, bone-seeking accumulation and retention can be proven by MRI in a rat model of focal malignant osteolysis. Meanwhile, we observed a whole-body distribution in the consecutive SPECT imaging after radiolabeling with I, SPECT imaging also indicated the enhanced bone tumor accumulation and prolonged retention. Resulting from the high drug loading and I labeling efficiency, the targeted nanomedicine exhibited significant chemotherapy and inter-radiotherapy capacity. Ultimately, the tumor burden of rats was obviously decreased except for the nontargeted group and the empty carrier group. In vivo CT imaging and pathological analysis revealed that the combined therapy was an efficient measure for antiosteolysis. Our findings suggest that albumin-based nanomedicine can provide a platform for bone-seeking diagnosis and therapeutic monitoring.

摘要

与不可逆转的原发性骨肿瘤和骨转移相关的恶性溶骨性疾病仍然是临床上急需解决的问题。利用灵活的纳米医学的成像和治疗功能,可以为恶性溶骨性疾病的治疗导航和监测提供一种替代方法。在这里,我们报告了载有阿霉素的基于白蛋白的氧化钆纳米粒子的开发,并与寻骨的阿仑膦酸钠缀合,用于靶向递药和治疗监测。与非靶向纳米药物相比,在局灶性恶性溶骨性疾病的大鼠模型中,可以通过 MRI 证明寻骨的聚集和保留。同时,我们在放射性标记碘后进行连续 SPECT 成像观察到全身分布,SPECT 成像也表明骨肿瘤的积累增强和保留时间延长。由于高载药量和 I 标记效率,靶向纳米药物表现出显著的化疗和放疗后治疗能力。最终,除了非靶向组和空载体组外,大鼠的肿瘤负担明显降低。体内 CT 成像和病理分析表明,联合治疗是一种有效的抗溶骨性治疗措施。我们的研究结果表明,基于白蛋白的纳米药物可为寻骨诊断和治疗监测提供一个平台。

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