Enhanced Antitumor Activity of Lapatinib Against Triple-Negative Breast Cancer Via Loading in Human Serum Albumin Publisher Pubmed



Rostaminasab S¹ ; Esmaeili A² ; Moosavimovahedi F² ; Memarkashani S² ; Rezaei Rudmianeh H² ; Shourian M¹ ; Shafiee Ardestani M³ ; Moosavimovahedi AA² ; Asghari SM² Show Affiliations
Source: International Journal of Biological Macromolecules Published:2024

Abstract

Triple-negative breast cancer (TNBC) presents significant treatment challenges due to its aggressive nature. Human serum albumin (HSA) is a promising drug delivery platform, offering high binding capacity, biocompatibility, and reduced toxicity. Lapatinib (LAP), a tyrosine kinase inhibitor for TNBC, is hindered by poor water solubility and toxicity. To address these issues, LAP was encapsulated within HSA (HSA-LAP), and its structural, drug release, and therapeutic properties were evaluated in cellular and animal TNBC models. HSA-LAP demonstrated efficient drug loading and pH-dependent tumor-targeted release, favoring acidic tumor microenvironments. Structural and microscopic studies confirmed LAP binding to HSA, with only minor structural and no significant morphological changes observed. In 4T1 breast cancer cells, HSA-LAP exhibited superior anti-proliferative, pro-apoptotic, and anti-migratory effects compared to free LAP, which were further amplified when combined with VGB3, a VEGFR1/2-targeting peptide, indicating an effective dual-targeting strategy for TNBC. In vivo, HSA-LAP showed greater tumor inhibition and improved survival rates, especially in combination with VGB3 through apoptosis induction. Biodistribution studies using technetium-99m (99mTc) labeling revealed enhanced tumor targeting. These findings highlight the potential of HSA as a delivery vehicle for LAP, particularly in combination with anti-angiogenic agents like VGB3, offering a promising therapeutic strategy for TNBC. © 2024 Elsevier B.V.