Enhanced antitumor activity of lapatinib against triple-negative breast cancer via loading in human serum albumin

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 4 T1 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-99 m (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.