Disordered Metal-Organic Frameworks for Drug Delivery

Project Information

DrugMOF

Grant agreement ID: 101107884

DOI

10.3030/101107884

Project closed

EC signature date 3 April 2023

Start date 1 September 2023

End date 31 August 2025

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 230 774,40

Coordinated by

AALBORG UNIVERSITET
Denmark

Periodic Reporting for period 1 - DrugMOF (Disordered Metal-Organic Frameworks for Drug Delivery)

Reporting period: 2023-09-01 to 2025-08-31

Summary of the context and overall objectives of the project

Modern medicine increasingly relies on targeted drug delivery systems to improve therapeutic outcomes while minimizing side effects. Conventional approaches often struggle to balance high drug loading with controlled release, a challenge that is particularly critical in cancer treatment where precise dosing can significantly impact patient safety and efficacy. Metal–organic frameworks (MOFs) have emerged as promising candidates due to their exceptional porosity and tunable chemistry, enabling them to store large amounts of drugs. However, their highly open crystalline structures typically lead to rapid drug release, which can cause harmful reactions and reduce treatment effectiveness.

The DrugMOF project attempted to address this gap by exploring disordered MOFs, specifically zeolitic imidazolate frameworks (ZIFs), as drug delivery platforms. Unlike their crystalline counterparts, disordered MOFs exhibited smaller pores and irregular structures that slowed down drug release. The strategy was therefore to first load drugs into crystalline ZIFs for maximum capacity, then transform these materials into amorphous or glassy states through processes such as ball milling or melt-quenching. This order-to-disorder transition combined the benefits of high loading with controlled release, creating biocompatible materials tailored for long-term therapeutic applications.

The overall objectives were threefold: (1) Develop and characterize ZIF-based systems capable of transitioning between crystalline and amorphous states while maintaining structural integrity and biocompatibility; (2) Demonstrate controlled drug release from these systems using model compounds, supported by in vitro cytotoxicity studies to ensure safety; and (3) Advance knowledge transfer and researcher training, fostering expertise in interdisciplinary fields spanning materials science, chemistry, and biomedicine.

This work aligned with EU priorities on health innovation and advanced materials, contributing to strategic goals of improving patient care and reducing healthcare costs in the long term. By enabling precise, sustained drug delivery, the project addressed pressing societal needs in oncology and chronic disease management. Beyond healthcare, the insights gained strengthened Europe’s leadership in functional materials research, supporting industrial translation and future collaborations.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

The DrugMOF project focused on developing advanced drug delivery systems using metal–organic frameworks (MOFs), particularly zeolitic imidazolate frameworks (ZIFs). The work combined material synthesis, structural characterization, and biological evaluation to address the challenge of achieving both high drug loading and controlled release.

The research focused on two ZIF materials (ZIF-8 and ZIF-62) using solvothermal and melt-quenching methods. These ZIFs were first prepared in their crystalline form to maximize drug loading capacity. Anti-cancer model drugs were incorporated into these structures, after which the materials were transformed into amorphous states through ball milling. This “order-to-disorder” approach successfully combined high drug storage with slow, sustained release.

Comprehensive analyses confirmed the structural integrity and functional properties of the materials. Techniques such as X-ray diffraction, Fourier-transform infrared spectroscopy, and Brunauer–Emmett–Teller (BET) surface area measurements revealed the transition from crystalline to amorphous states and its impact on porosity. Drug encapsulation was verified using UV–Vis spectroscopy and thermogravimetric analysis, while microscopy and X-ray photoelectron spectroscopy provided insights into particle size and surface chemistry.

In vitro studies demonstrated that crystalline ZIFs released most of the drug within days, whereas amorphous forms achieved prolonged release over several weeks. Cytotoxicity tests using HeLa cells confirmed that both crystalline and amorphous ZIFs were, at least partially, biocompatible, with drug-loaded samples showing high cell viability. These findings validate the potential of disordered MOFs for safe and efficient drug delivery.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

The DrugMOF project has delivered results of relevance for drug delivery. Traditional systems often face a trade-off: materials that can store large amounts of drugs tend to release them too quickly, while those that release drugs slowly usually have low loading capacity. Building on earlier work in the field, DrugMOF addresses this barrier by introducing a order-to-disorder strategy using metal–organic frameworks (MOFs), specifically zeolitic imidazolate frameworks (ZIFs).

The project demonstrated that crystalline ZIFs can achieve high drug loading, and when converted into amorphous or glassy forms, they enable sustained release over weeks. That is, controlled release results showed that amorphous ZIF-8 and ZIF-62 significantly slow drug diffusion compared to their crystalline counterparts, achieving controlled release for more than 20 days. Cytotoxicity tests confirmed that both crystalline and amorphous forms have potential for biological use, paving the way for clinical translation in future work.

These findings could open new possibilities for cancer therapy and chronic disease management, where precise dosing and long-term release are critical. By reducing dosing frequency and minimizing side effects, these materials could improve patient compliance and treatment outcomes. Beyond healthcare, the methodology for creating MOF-derived glasses may inspire innovations in other fields, such as sensors and catalysis. Further research and demonstration could focus on clinical studies and long-term biocompatibility tests to validate safety and efficacy.