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

Q: What problem does the study target in conventional chemotherapy?

It addresses poor solubility, off-target toxicity, and multidrug resistance that limit conventional chemotherapy effectiveness.

Q: How were LAP@ZIF-8 nanoparticles synthesized and what key loading metrics were achieved?

They were prepared via facile one-pot synthesis, achieving 72.4% encapsulation efficiency and 6.6% drug loading capacity.

Q: How does LAP@ZIF-8 release depend on pH?

Drug release was pH-responsive, reaching 77% cumulative release at pH 5.5 compared with 43% at pH 7.4 after 96 hours.

Sep 29, 2026

Upload by วิน

Conventional chemotherapy suffers from poor solubility, off-target toxicity, and multidrug resistance, motivating nanoparticle-based delivery systems. This work reports facile one-pot synthesis of lapatinib-encapsulated ZIF-8 nanoparticles (LAP@ZIF-8) with 72.4% encapsulation efficiency and 6.6% drug loading. Characterization confirmed uniform hexagonal morphology, 236 ± 2 nm hydrodynamic size, +29 mV surface charge, strong crystallinity, and excellent thermal stability. pH-responsive release reached 77% cumulative release at pH 5.5 versus 43% at pH 7.4 after 96 h, with <11% serum-protein binding and <2% hemolysis.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Abstract

1. Introduction

This article is licensed under CC-BY 4.0 [http://pubs.acs.org/journal/acsodf](http://pubs.acs.org/journal/acsodf) Article Lapatinib-Loaded ZIF‑8 Nanoparticles: A Multifunctional Drug Delivery System with Anticancer, Antibacterial, and Antioxidant Properties Ezgi Aslan and G̈ulah anlı-Mohamed* Cite This: ACS Omega 2025, 10, 58175−58193 Read Online | | | | | | --- | --- | --- | --- | | ACCESS | Metrics & More | | Article Recommendations | 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 exclent 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. 1. INTRODUCTION Cancer remains a significant global health issue, with its prevalence and associated mortality rates increasing over time. Breast cancer, which accounted for 11.7% of all cancer cases worldwide in 2020, 1 became the second most common cancer globally in 2022, representing 11.6% of cases. Among women, breast cancer remains the most frequently diagnosed malignancy.2 The overexpression of human epidermal growth factor receptor 2 (HER2), an oncogene that regulates cell growth and differentiation,3 is observed in approximately 20−25% of breast cancer cases and is associated with aggressive disease progression.4 Lapatinib (LAP; GW 572016; Tykerb, GlaxoSmithKline), the first dual inhibitor targeting the epidermal growth factor receptor (EGFR/HER1) and HER2/erythroblastic leukemia viral oncogene homologue 2 (ErbB2) tyrosine kinases was approved by the U.S. Food and Drug Administration (FDA) in 2007.5 LAP, a hydrophobic compound with low water solubility (approximately core structure.6 0.007 mg/mL), is derived from the quinazoline Despite its therapeutic effectiveness, LAP’s poor water solubility significantly reduces its intestinal absorption and bioavailability while also causing damage to the gastrointestinal tract, limiting its use as an injectable drug. This challenge has underscored the need for nanoparticle-based delivery systems to enhance its solubility and therapeutic efficacy.7 Moreover, most anticancer drugs lack specificity between cancerous and normal cells, leading to systemic toxicity and adverse effects.8 The limitations of current cancer therapies, including severe side effects and dru

FAQs

What problem does the study target in conventional chemotherapy?

It addresses poor solubility, off-target toxicity, and multidrug resistance that limit conventional chemotherapy effectiveness.

How were LAP@ZIF-8 nanoparticles synthesized and what key loading metrics were achieved?

They were prepared via facile one-pot synthesis, achieving 72.4% encapsulation efficiency and 6.6% drug loading capacity.

How does LAP@ZIF-8 release depend on pH?

Drug release was pH-responsive, reaching 77% cumulative release at pH 5.5 compared with 43% at pH 7.4 after 96 hours.

Sep 29, 2026

Upload by วิน