Pham Thanh Minh, Cao Dong Vu, Dang Ho Hong Quang, Mai Phuoc Minh Thanh, Nguyen Thanh Binh, Dinh Ngoc Bao Nam, Nguyen Thi Khanh Giang, Le Thi Mai Huong, Doan Van Dat, Nguyen Duc Thuan, Le Van Thuan
Dalat Nuclear Research Institute, 01 Nguyen Tu Luc, Dalat, 670000, Vietnam.
Nuclear Training Center, Vietnam Atomic Energy Institute, 140 Nguyen Tuan Street, Thanh Xuan District, Hanoi, 110430, Vietnam.
J Mater Chem B. 2024 Jan 17;12(3):678-690. doi: 10.1039/d3tb01957h.
The present study introduces FeO-coated lapatinib-labeled Sm nanoparticles (denoted as FeO@lapatinib-Sm) as a promising avenue for advancing breast cancer treatment. The radiolabeled nanoparticles combine various attributes, offering enhanced therapeutic precision. The integration of lapatinib confers therapeutic effects and targeted delivery. The inherent magnetic characteristics of FeO nanoparticles contribute to improved imaging contrast and targeted localization. Incorporating the gamma-emitting Sm isotope permits single-photon emission computed tomography imaging and radiation dose evaluation, while its beta-emitting nature ensures targeted cancer cell eradication. The synthesis of FeO@lapatinib-Sm was meticulously optimized by investigating the effects of parameters on radiolabeling efficiency. Physicochemical attributes were scrutinized using several analytical techniques. In-depth assessment evaluated the biocompatibility, toxicity, and biodistribution in a murine model, illuminating clinical utility. Optimal conditions (SmCl concentration of 10 mCi mL, pH 7.4, a reaction time of 30 min, and a temperature of 25 °C) achieved >99% labeling efficiency and radiochemical purity. The TEM analysis indicated that the diameter of FeO@lapatinib-Sm nanoparticles ranged from 10 to 40 nm. Vibrating-sample magnetometry verified their superparamagnetic behaviour with a saturation magnetization of 41.4 emu g. The synthesized radiopharmaceutical exhibited high sterility and stability. Acute toxicity studies showed the mild effects of FeO@lapatinib-Sm at a dose of 20 mCi kg, with no observed mortality. Notably, lesions from FeO@lapatinib-Sm use recovered naturally over time. Radiation doses below 20 mCi kg were recommended for clinical trials. The biodistribution study in BT474 xenograft mice revealed rapid clearance of FeO@lapatinib-Sm within 48 h. Significant accumulation occurred in the liver, spleen, and tumor tissue, while minimal accumulation was found in other tissues. Future steps involve studying biocorona formation and therapeutic efficacy on tumour models, refining its clinical potential.
本研究引入了包覆FeO的拉帕替尼标记的钐纳米颗粒（记为FeO@拉帕替尼-钐），作为推进乳腺癌治疗的一条有前景的途径。放射性标记的纳米颗粒结合了多种特性，提供了更高的治疗精度。拉帕替尼的整合赋予了治疗效果和靶向递送能力。FeO纳米颗粒固有的磁性特征有助于改善成像对比度和靶向定位。掺入发射γ射线的钐同位素可进行单光子发射计算机断层扫描成像和辐射剂量评估，而其发射β射线的特性可确保靶向根除癌细胞。通过研究参数对放射性标记效率的影响，精心优化了FeO@拉帕替尼-钐的合成。使用多种分析技术仔细研究了其物理化学特性。深入评估在小鼠模型中评估了生物相容性、毒性和生物分布，阐明了其临床应用价值。最佳条件（SmCl浓度为10 mCi/mL，pH值为7.4，反应时间为30分钟，温度为25°C）实现了>99%的标记效率和放射化学纯度。透射电子显微镜分析表明，FeO@拉帕替尼-钐纳米颗粒的直径范围为10至40纳米。振动样品磁强计验证了它们的超顺磁性行为，饱和磁化强度为41.4 emu/g。合成的放射性药物表现出高无菌性和稳定性。急性毒性研究表明，剂量为20 mCi/kg时，FeO@拉帕替尼-钐的影响轻微，未观察到死亡。值得注意的是，使用FeO@拉帕替尼-钐造成的损伤会随着时间自然恢复。建议临床试验的辐射剂量低于20 mCi/kg。在BT474异种移植小鼠中的生物分布研究表明，FeO@拉帕替尼-钐在48小时内迅速清除。在肝脏、脾脏和肿瘤组织中发生了显著积累，而在其他组织中积累极少。未来的步骤包括研究生物冠形成及其对肿瘤模型的治疗效果，完善其临床潜力。
Cochrane Database Syst Rev. 2020-10-19
Health Technol Assess. 2006-9
Cochrane Database Syst Rev. 2021-4-19
Cochrane Database Syst Rev. 2005-7-20
Zotero 插件