Lapatinib-Loaded Glucose-Functionalized Silver Nanoparticles Enhance Efficacy in HER2-Positive Breast Cancer Cells and Modulate Survival-Associated Genes.

BACKGROUND

Lapatinib is a dual EGFR/HER2 tyrosine kinase inhibitor used in HER2-positive breast cancer (BC). Here, we identified prognostic genes modulated by lapatinib and evaluated whether glucose-functionalized, lapatinib-conjugated silver nanoparticles could enhance its anticancer efficacy.

METHODS

Lapatinib-responsive genes were identified from the GSE38376 dataset and their prognostic associations were assessed using The Cancer Genome Atlas (TCGA). Silver nanoparticles were synthesized by Spirulina-mediated reduction of AgNO₃, functionalized with glucose, and conjugated to lapatinib (Ag@Glu-Lapatinib NP), then characterized by FTIR, XRD, zeta potential, SEM, and TEM. SKBR3 cells were treated with Ag@Glu-Lapatinib NP, Ag NP, or lapatinib and evaluated by MTT, Annexin V/PI apoptosis assay, and RT-qPCR for candidate genes.

RESULTS

Transcriptomic analysis indicated that lapatinib suppresses proliferation-associated genes and enriches apoptosis-related pathways. In TCGA, ECE2 and CDCA5 were overexpressed and associated with poorer outcomes, whereas PDK4 and ALDH1A1 were reduced and linked to favorable prognosis. Ag@Glu-Lapatinib NP formation was confirmed, and the nanoformulation showed higher potency (IC₅₀ = 62 μg/mL at 24 h; 31 μg/mL at 48 h) than free lapatinib (250 μg/mL) or Ag NP (125 μg/mL), with markedly increased apoptosis. RT-qPCR verified significant modulation of ECE2, CDCA5, PDK4, and ALDH1A1 after Ag@Glu-Lapatinib NP treatment.

CONCLUSION

Conjugating lapatinib to glucose-functionalized silver nanoparticles enhances its activity in HER2-positive BC cells and modulates survival-associated genes. This nano-therapeutic strategy may strengthen the therapeutic potential of lapatinib in breast cancer.