153Sm-labeled Fe3O4@lapatinib nanoparticles as a potential therapeutic agent for breast cancer: synthesis, quality control, and in vivo evaluation

Abstract

The present study introduces Fe₃O₄-coated lapatinib-labeled ¹⁵³Sm nanoparticles (denoted as Fe₃O₄@lapatinib-¹⁵³Sm) 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 Fe₃O₄ nanoparticles contribute to improved imaging contrast and targeted localization. Incorporating the gamma-emitting ¹⁵³Sm 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 Fe₃O₄@lapatinib-¹⁵³Sm was meticulously optimized by investigating the effects of parameters on radiolabeling efficiency. Physicochemical attributes were scrutinized using several analytical techniques. In-depth in vivo assessment evaluated the biocompatibility, toxicity, and biodistribution in a murine model, illuminating clinical utility. Optimal conditions (¹⁵³SmCl₃ concentration of 10 mCi mL⁻¹, 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 Fe₃O₄@lapatinib-¹⁵³Sm nanoparticles ranged from 10 to 40 nm. Vibrating-sample magnetometry verified their superparamagnetic behaviour with a saturation magnetization of 41.4 emu g⁻¹. The synthesized radiopharmaceutical exhibited high sterility and in vitro stability. Acute toxicity studies showed the mild effects of Fe₃O₄@lapatinib-¹⁵³Sm at a dose of 20 mCi kg⁻¹, with no observed mortality. Notably, lesions from Fe₃O₄@lapatinib-¹⁵³Sm use recovered naturally over time. Radiation doses below 20 mCi kg⁻¹ were recommended for clinical trials. The biodistribution study in BT474 xenograft mice revealed rapid clearance of Fe₃O₄@lapatinib-¹⁵³Sm 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.