Lapatinib-Loaded ZIF‑8 Nanoparticles: A Multifunctional Drug Delivery System with Anticancer, Antibacterial, and...

The pitfalls of conventional chemotherapy, including poor solubility, off-target toxicity, and multidrug resistance, have driven the development of nanoparticle-based delivery systems. Here, we report the facile one-pot synthesis of lapatinib-encapsulated zeolitic imidazolate framework-8 (LAP@ZIF-8) nanoparticles. The formulation achieved an encapsulation efficiency of 72.4% and a drug loading capacity of 6.6%. Comprehensive physicochemical characterization confirmed uniform hexagonal morphology (SEM), favorable hydrodynamic size (236 ± 2 nm; DLS), positive surface charge (+29 mV; ζ-potential), high crystallinity (XRD), and excellent thermal stability (TGA). LAP release was pH-responsive, with ∼77% cumulative release at pH 5.5 (tumor-mimicking) versus 43% at pH 7.4 after 96 h. Serum-protein binding (<11%) and hemolysis (<2%) assays demonstrated good biocompatibility. In vitro, LAP@ZIF-8 exhibited potent, selective cytotoxicity toward HER2-positive SK-BR-3 breast-cancer cells (72 h IC₅₀ = 1.2 μg mL^-1) while sparing HER2-negative MCF-7 cells. Importantly, both free LAP and LAP@ZIF-8 were well-tolerated by nontumorigenic MCF-10A mammary epithelial cells: viability remained ≥90% at ≤1 μg mL^-1 and exceeded 50% even at 100 μg mL^-1, indicating that the IC₅₀ was not reached and providing a preliminary safety window for healthy tissues. Beyond its anticancer effects, the nanocarrier displayed broad-spectrum antibacterial activity (minimum bactericidal concentrations: 5 mg mL^-1 for Staphylococcus aureus and 10 mg mL^-1 for Escherichia coli) and moderate antioxidant capacity (DPPH IC₅₀ = 666 μg mL^-1). Collectively, these results position LAP@ZIF-8 as a versatile, pH-sensitive platform that combines selective anticancer efficacy with low toxicity to healthy cells alongside ancillary antibacterial and antioxidant properties suitable for multimodal therapy.