Tocopherol-human serum albumin nanoparticles enhance lapatinib delivery and overcome doxorubicin resistance in breast cancer

Introduction: HER2, a tyrosine kinase receptor, is amplified in HER2-positive breast cancer, driving cell signaling and growth. Aim: This study aimed to combat multidrug resistance in Dox-insensitive breast adenocarcinoma by creating a nanoformulation therapy with a tyrosine kinase inhibitor. Methodology: Human serum albumin (HSA) was conjugated with α-D-tocopherol succinate to form nanoaggregates loaded with lapatinib (Lapa). Results: The resulting Lapa@HSA(VE) NPs were 117.2 nm in size and demonstrated IC50 values of 10.25 μg/ml on MCF7 (S) and 8.02 μg/ml on MCF7 (R) cell lines. Conclusion: Lapa@HSA(VE) NPs showed no hepatotoxicity, unlike free Lapa, as seen in acute toxicity studies in rats.
α-D-tocopherol succinate (vitamin E) was conjugated to human serum albumin (HSA).
The HSA-VE conjugate formed nanoparticles (NPs) by self-assembly without any external cross-linker and loaded Lapatinib (Lapa).
The NPs were characterized thoroughly.
Time-dependent uptake of NPs was observed in tested sensitive and resistant human breast cancer cell lines (MCF-7).
The nanomedicine displayed enhanced cytotoxicity in breast cancer cell lines compared with free drugs at higher concentrations.
Lapa@HSA(VE) NPs caused significantly higher reactive oxygen species (ROS) generation and mitochondrial depolarization in tested breast cancer cell lines compared with free Lapa.
In vivo pharmacokinetic data showed sustained drug release from nanoformulation with decreased systemic clearance, and in vivo, toxicity study revealed that the nanoformulation considerably reduced hepatotoxicity compared with free Lapa.