In Vivo Bioorthogonal Radiolabeling of Nanoparticles to Minimize Liver Radiation.

IF 9.6 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Yun Gao, Xiaotong Wang, Can Chen, Lei Chen, Xiaoyi Cao, Mengyao Wu, Yi Zhou, Jianfeng Zeng, Mingyuan Gao
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Abstract

Radiolabeled nanoparticles hold great promise in precision medicine due to its versatile applications in disease imaging and therapy. However, its clinical translation is often hindered by excessive accumulation in reticuloendothelial system organs, particularly the liver, which can lead to radiation-induced toxicity. Herein, an in vivo selective radiolabeling strategy is reported that exploits the distinct subcellular fates of nanoparticles in tumors versus liver. A biorthogonal nanosystem composed of trans-cyclooctene (TCO)-functionalized iron oxide nanoparticles (Fe3O4@TCO) and a radiolabeled tetrazine probe (177Lu-DOTA-Tz) is constructed to validate this concept. Owing to the hydrophilic nature, 177Lu-DOTA-Tz cannot penetrate cell membranes, resulting in spatially restricted bioorthogonal labeling in the extracellular space. At tumor sites, Fe3O4@TCO nanoparticles accumulate via the enhanced permeability and retention effect and remain accessible for efficient binding with 177Lu-DOTA-Tz. In contrast, in the liver, nanoparticles are predominantly internalized by liver cells, and its intracellular localization prevents interaction with the probe, thereby minimizing hepatic radiation retention. By harnessing these subcellular distribution differences, the approach achieves selective in vivo radiolabeling and significantly improves the tumor-to-liver radiation ratio. This study provides a biologically informed strategy for designing radiolabeled nanoplatforms with enhanced safety profiles for theranostic applications.

纳米颗粒体内生物正交放射性标记以减少肝脏辐射。
放射标记纳米粒子由于其在疾病成像和治疗中的广泛应用,在精密医学中具有很大的前景。然而,其临床转化往往受到网状内皮系统器官,特别是肝脏过度积累的阻碍,这可能导致辐射诱导的毒性。本文报道了一种体内选择性放射性标记策略,利用纳米颗粒在肿瘤和肝脏中不同的亚细胞命运。为了验证这一概念,构建了由反式环烯(TCO)功能化氧化铁纳米粒子(Fe3O4@TCO)和放射性标记四氮探针(177Lu-DOTA-Tz)组成的双正交纳米体系。由于其亲水性,177Lu-DOTA-Tz不能穿透细胞膜,导致细胞外空间的生物正交标记受到空间限制。在肿瘤部位,Fe3O4@TCO纳米颗粒通过增强的渗透性和滞留效应积累,并保持与177Lu-DOTA-Tz有效结合。相反,在肝脏中,纳米颗粒主要被肝细胞内化,其细胞内定位防止了与探针的相互作用,从而最大限度地减少了肝脏辐射滞留。通过利用这些亚细胞分布差异,该方法实现了选择性体内放射性标记,并显着提高了肿瘤与肝脏的放射比。这项研究为设计具有更高安全性的放射标记纳米平台提供了生物学信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Advanced Healthcare Materials
Advanced Healthcare Materials 工程技术-生物材料
CiteScore
14.40
自引率
3.00%
发文量
600
审稿时长
1.8 months
期刊介绍: Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.
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