Ozgenc Emre, Karpuz Merve, Arzuk Ege, Gonzalez-Alvarez Marta, Sanz Marival Bermejo, Gundogdu Evren, Gonzalez-Alvarez Isabel
Department of Radiopharmacy, Ege University, 35040, Izmir, Turkey.
Department of Radiopharmacy, Izmir Katip Celebi University, 35620, Izmir, Turkey.
ACS Omega. 2022 Aug 19;7(34):30015-30027. doi: 10.1021/acsomega.2c03023. eCollection 2022 Aug 30.
Radiolabeled trastuzumab (TRZ) loaded solid lipid nanoparticles (SLNs) were prepared by high shear homogenization and sonication techniques. The apoptosis mechanism of TRZ-SLNs was studied only with the MCF-7 cell line, while the cytotoxicity and cell binding capacity were investigated using breast cancer cells (MCF-7 and MDA-MB-231) and the human keratinocyte cell line (HaCaT). The particle sizes of TRZ-SLNs were found to be below 100 nm, and they possessed a negative charge. The high radiolabeling efficiency and good radiolabeling stability in saline and a cell culture medium were obtained in the results of radiolabeling studies. According to the in vitro studies, TRZ-SLNs were found to be biocompatible, and they effectively induced apoptosis in MCF-7 cells. After the parenteral injection of TRZ-SLNs into rats, a sustained release profile in blood circulation was achieved compared with free drug solution by the evaluation of pharmacokinetic parameters. As a conclusion, the study reveals that Technetium-99m (Tc radiolabeled) TRZ loaded SLN formulations could be promising theranostic agents based on their characterization profiles, in vitro cellular uptake and apoptosis induction capacity, and in vivo pharmacokinetic profiles.
通过高剪切均质化和超声处理技术制备了负载放射性标记曲妥珠单抗（TRZ）的固体脂质纳米粒（SLN）。仅使用MCF-7细胞系研究了TRZ-SLN的凋亡机制，而使用乳腺癌细胞（MCF-7和MDA-MB-231）和人角质形成细胞系（HaCaT）研究了细胞毒性和细胞结合能力。发现TRZ-SLN的粒径低于100 nm，并且带有负电荷。放射性标记研究结果表明，在生理盐水和细胞培养基中具有高放射性标记效率和良好的放射性标记稳定性。根据体外研究，发现TRZ-SLN具有生物相容性，并且能有效诱导MCF-7细胞凋亡。通过评估药代动力学参数，与游离药物溶液相比，将TRZ-SLN经肠胃外注射到大鼠体内后，在血液循环中实现了缓释。总之，该研究表明，基于其表征特征、体外细胞摄取和凋亡诱导能力以及体内药代动力学特征，99m锝（Tc放射性标记）负载TRZ的SLN制剂有望成为治疗诊断剂。
