Bone-Seeking Albumin-Nanomedicine for In Vivo Imaging and Therapeutic Monitoring
Bone-Seeking Albumin-Nanomedicine for In Vivo Imaging and Therapeutic Monitoring
复制标题
DOI：
10.1021/acsbiomaterials.9b01195
复制
发表时间：
2020-01-01
影响因子：
5.8
通讯作者：
Wang, Yangyun
中科院分区：
文献类型：
--
作者：
Chen, Zhizhong;Yu, Hongchang;Wang, Yangyun
与不可逆的原发性骨肿瘤和骨转移相关的恶性骨溶解仍然是临床上紧迫的问题。利用柔性纳米医学的成像和治疗功能可以为恶性骨溶解的治疗导航和监测提供替代方案。在这里，我们报告了基于白蛋白的氧化钆纳米颗粒的开发，该纳米颗粒负载阿霉素并与骨寻源阿仑膦酸盐缀合，用于靶向递送和治疗监测。与非靶向纳米药物相比，在局灶性恶性骨质溶解的大鼠模型中，MRI 可以证明寻骨的积累和保留。同时，我们在连续SPECT成像中观察到1231放射性标记后的全身分布，SPECT成像也表明骨肿瘤积累增强和保留时间延长。由于高载药量和 I-131 标记效率，靶向纳米药物表现出显着的化疗和放疗间能力。最终，除非靶向组和空载体组外，大鼠的肿瘤负荷均明显降低。体内CT成像和病理分析表明联合治疗是一种有效的抗骨溶解措施。我们的研究结果表明，基于白蛋白的纳米医学可以为寻骨诊断和治疗监测提供平台。
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 1231, SPECT imaging also indicated the enhanced bone tumor accumulation and prolonged retention. Resulting from the high drug loading and I-131 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.