pH-Responsive Delivery of Nonsteroidal Anti-Inflammatory Drugs by ZIF-8 Metal-Organic Frameworks for Cancer Treatment
- 1University of L’Aquila , , via Vetoio (“A.C. De Meis” building) , Coppito, ,
- 2Consorzio INSTM UdR L’Aquila , via Vetoio (“A.C. De Meis” building) , Coppito, ,
Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) have attracted increasing attention as potential anticancer agents due to their ability to inhibit cyclooxygenase-mediated inflammatory pathways involved in tumor progression. However, their clinical use in oncology remains limited by poor tumor selectivity and systemic toxicity. In this work, we investigate zeolitic imidazolate framework-8 (ZIF-8) nanoparticles as pH-responsive carriers for the delivery of different NSAIDs with potential anticancer activity. A loading strategy based on the conversion of the drugs into their sodium salts, followed by ultrasound-assisted encapsulation, was developed to preserve the structural integrity of the MOF while achieving efficient drug incorporation. Structural and textural characterization by XRPD, SEM, ATR-MIR spectroscopy, and nitrogen physisorption confirmed the formation of ZIF-8 nanoparticles with an average size of about 150 nm and the successful encapsulation of the drugs within the porous framework. High-performance liquid chromatography revealed drug-loading efficiencies exceeding 80% for selected formulations. Release studies demonstrated a pronounced pH-dependent behavior, with significantly faster drug release under mildly acidic conditions that mimic the tumor microenvironment. The biological activity of selected formulations was evaluated in prostate-derived cell models (BPH, LNCaP, and DU145), revealing enhanced cytotoxicity toward cancer cells under acidic conditions compared to physiological pH. In particular, naproxen@ZIF-8 showed a marked reduction in DU145 cell viability at low concentrations and under mildly acidic conditions. These results highlight the potential of ZIF-8 as a versatile nanoplatform for the controlled and tumor-responsive delivery of anti-inflammatory drugs with an anticancer activity.
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BibTeX
@article{nicola2026phresponsive,
title = {{pH-Responsive Delivery of Nonsteroidal Anti-Inflammatory Drugs by ZIF-8 Metal-Organic Frameworks for Cancer Treatment}},
author = {Nicola di Nicola and Mauro Di Vito Nolfi and Alice Vetrano and Jennifer Esposito and Patrizio Campitelli and Alessia Marino and Francesca Zazzeroni and Leonardo Guidoni and Marcello Crucianelli and Davide Vecchiotti and Andrea Lazzarini},
journal = {ACS Omega},
year = {2026},
month = oct,
doi = {10.1021/acsomega.6c06939},
url = {https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c06939/5455487/pH-Responsive-Delivery-of-Nonsteroidal-Anti},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - pH-Responsive Delivery of Nonsteroidal Anti-Inflammatory Drugs by ZIF-8 Metal-Organic Frameworks for Cancer Treatment
AU - Nicola di Nicola
AU - Mauro Di Vito Nolfi
AU - Alice Vetrano
AU - Jennifer Esposito
AU - Patrizio Campitelli
AU - Alessia Marino
AU - Francesca Zazzeroni
AU - Leonardo Guidoni
AU - Marcello Crucianelli
AU - Davide Vecchiotti
AU - Andrea Lazzarini
PY - 2026
DA - 2026/10/21
JO - ACS Omega
DO - 10.1021/acsomega.6c06939
UR - https://pubs.acs.org/acsodf/article/doi/10.1021/acsomega.6c06939/5455487/pH-Responsive-Delivery-of-Nonsteroidal-Anti
AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) have attracted increasing attention as potential anticancer agents due to their ability to inhibit cyclooxygenase-mediated inflammatory pathways involved in tumor progression. However, their clinical use in oncology remains limited by poor tumor selectivity and systemic toxicity. In this work, we investigate zeolitic imidazolate framework-8 (ZIF-8) nanoparticles as pH-responsive carriers for the delivery of different NSAIDs with potential anticancer activity. A loading strategy based on the conversion of the drugs into their sodium salts, followed by ultrasound-assisted encapsulation, was developed to preserve the structural integrity of the MOF while achieving efficient drug incorporation. Structural and textural characterization by XRPD, SEM, ATR-MIR spectroscopy, and nitrogen physisorption confirmed the formation of ZIF-8 nanoparticles with an average size of about 150 nm and the successful encapsulation of the drugs within the porous framework. High-performance liquid chromatography revealed drug-loading efficiencies exceeding 80% for selected formulations. Release studies demonstrated a pronounced pH-dependent behavior, with significantly faster drug release under mildly acidic conditions that mimic the tumor microenvironment. The biological activity of selected formulations was evaluated in prostate-derived cell models (BPH, LNCaP, and DU145), revealing enhanced cytotoxicity toward cancer cells under acidic conditions compared to physiological pH. In particular, naproxen@ZIF-8 showed a marked reduction in DU145 cell viability at low concentrations and under mildly acidic conditions. These results highlight the potential of ZIF-8 as a versatile nanoplatform for the controlled and tumor-responsive delivery of anti-inflammatory drugs with an anticancer activity.
SN - 2470-1343
ER -