Radiolabeled Trastuzumab Solid Lipid Nanoparticles for Breast Cancer Cell: in Vitro and in Vivo Studies

Emre Ozgenc; Merve Karpuz; Ege Arzuk; Marta Gonzalez-Alvarez; Marival Bermejo Sanz; Evren Gundogdu; Isabel Gonzalez-Alvarez

doi:10.1021/acsomega.2c03023

Radiolabeled Trastuzumab Solid Lipid Nanoparticles for Breast Cancer Cell: in Vitro and in Vivo Studies

ACS Omega. 2022 Aug 19;7(34):30015-30027. doi: 10.1021/acsomega.2c03023. eCollection 2022 Aug 30.

Authors

Emre Ozgenc¹, Merve Karpuz², Ege Arzuk³, Marta Gonzalez-Alvarez⁴, Marival Bermejo Sanz⁴, Evren Gundogdu¹, Isabel Gonzalez-Alvarez⁴

Affiliations

¹ Department of Radiopharmacy, Ege University, 35040, Izmir, Turkey.
² Department of Radiopharmacy, Izmir Katip Celebi University, 35620, Izmir, Turkey.
³ Department of Toxicology, Faculty of Pharmacy, Ege University, 35040, Izmir, Turkey.
⁴ Department of Pharmacokinetics and Pharmaceutical Technology, Miguel Hernandez University, San Juan de Alicante, 03550 Elche, Alicante, Spain.

Abstract

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 (^99mTc 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.