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

## TL;DR

Researchers developed a new nanoparticle system that delivers lapatinib, a cancer drug, with improved cancer targeting, low toxicity, and additional antibacterial and antioxidant effects.

## Contribution

A novel pH-responsive nanoparticle system (LAP@ZIF-8) with combined anticancer, antibacterial, and antioxidant properties is introduced.

## Key findings

- LAP@ZIF-8 showed 72.4% drug encapsulation and pH-dependent release, with 77% release at tumor-like pH.
- The nanoparticles selectively killed HER2-positive breast cancer cells while sparing healthy cells.
- LAP@ZIF-8 exhibited antibacterial activity against S. aureus and E. coli and moderate antioxidant capacity.

## Abstract

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.