Precise drug delivery to enhance therapeutic effectiveness
Researchers in the HeatNMof project are developing innovative new materials to deliver drugs precisely to anatomical locations within the human body. These novel materials are designed primarily for cancer therapies, offering the potential to enhance therapeutic effectiveness while mitigating treatment-associated adverse effects, writes Patricia Horcajada
The nanomedicine sector is experiencing rapid expansion, and research into new materials and technologies designed to improve cancer treatment and aid drug delivery continues apace. Metal-Organic Frameworks (MOFs), a class of ordered porous multifunctional materials, hold great potential in drug delivery, in large part due to their porosity and structural versatility. This adaptability, driven by the tunable structural and chemical properties of MOFs, allows for their application across a broad spectrum of domains, including therapeutics delivery to treat different types of cancer.
HeatNMof project
This topic constitutes the focal point of the HeatNMof project, an EU innovative training network that amalgamated partners from the academic and industrial sectors to develop new materials for application in nanomedicine. Within this context, a consortium of researchers endeavoured to create novel materials tailored for the treatment of diverse cancer types, including pancreatic, breast, and glioblastoma. The project notably underscored the synthesis and characterization of MOFs, materials well-suited for the targeted delivery
of pharmaceutical agents to a specific site in the body. The high surface area of these MOFs means they can be loaded with substantial amounts of drugs, while their adjustable porosity facilitates controlled release kinetics, a pivotal feature for delivering drugs precisely to the intended site of action. Precise drug delivery helps maximise therapeutic effectiveness by enhancing the efficacy of the payload and reducing potential side effects.
“Metal-Organic
researchers have engaged in the synthesis of nanoscaled-MOFs (nanoMOFs) and MOF nanocomposites to achieve this objective. In particular, the development of nanocomposites involved the incorporation of inorganic particles, such as plasmonic or magnetic nanoparticles, to confer specific capabilities upon the MOFs.
Indeed, the integration of inorganic nanoparticles facilitates the trigger release
Frameworks
, a class of ordered porous multifunctional materials, hold great potential in drug delivery, in large part due to their porosity and structural versatility.”
The consortium worked to both develop new MOFs and modify existing ones, as well as to enhance their functionalities. A major priority in the project was engineering MOFs for targeted drug delivery, which involved tailoring the pore size, surface functionality, and structural integrity of the different MOFs to align with the physicochemical properties of certain drugs. Moreover, the project’s agenda also encompassed an exploration of material interactions at the nanoscale. Consequently,
mechanism. Notably, two primary stimulilight and magnetic fields - have been explored in terms of their potential to precisely trigger drug release from the nanocomposites at targeted sites within the body, such as tumours. These stimuli could produce a thermal or mechanical effect conducive to the controlled release of encapsulated drugs precisely at sites where they exert maximal therapeutic benefits, thus limiting their impact on healthy cells.
Materials testing
The materials developed within the project have been meticulously tested with respect to their efficacy as drug delivery systems, with researchers striving for precision in treatment delivery and effectiveness. A variety of pharmaceutical agents, including doxorubicin, 5-fluorouracil, oxaliplatin, cisplatin, and gemcitabine, have been employed, either individually or in combination with each other (two drugs within the same carrier). Such research endeavours hold the promise of broadening the therapeutic repertoire available for various medical conditions.
The pursuit of a more refined approach to drug delivery, enabling precise localization within the body, holds the potential to facilitate the utilization of more potent pharmaceuticals against specific conditions, while minimizing collateral damage to surrounding healthy tissue. Moreover, the ability to administer multiple drugs utilizing a single carrier could also lead to synergistic effects, wherein the combined therapeutic efficacy is greater than the effects of individual drug entities. This opens up new avenues for addressing diseases that are currently difficult to manage with single-drug therapies.
The implications of the project’s research extend beyond the realm of the drugs and conditions that have been directly investigated. By demonstrating the feasibility and benefits of targeted and combination drug delivery using MOF composites, the project has inspired further research in this area, paving the way for the development of new treatments for a wide range of diseases. Further collaborations are planned and followup projects have been proposed, illustrating the promise of this field of research and its potential impact on medical treatment. This is further underlined by broader interest in the project’s endeavours, with commercial partners having played a pivotal role in shaping and guiding the research. While the pathway towards commercialization and eventual clinical implementation of these materials is multifaceted, the HeatNMOF project has laid crucial groundwork for advancing them to higher Technology
HeatNMof
Heating triggered drug release from nanometric inorganic – metal-organic framework composites
Project Objectives
Annual project meeting 2022.
Readiness Levels (TRLs). The consortium has identified several interesting potential avenues of investigation, including the refinement of advanced MOF composites and combination therapies.
The Early Stage Researchers (ESRs) themselves hold potential significance in this ongoing research, whether they opt to pursue careers within academia or transition into the commercial sector. The project provided a comprehensive training program, designed to equip the ESRs with a variety of skills tailored to the highly competitive job landscape. Through secondments at partner institutions within the commercial sector, ESRs gained invaluable hands-on experience and insights into industrial practices. This bridging of the gap between theoretical insights and practical applications is crucial for translating innovative research into tangible advancements in treatment modalities. ESRs gained a broader perspective, which encouraged innovative thinking and the development of problemsolving skills applicable across both academic and commercial domains. The opportunity to collaborate across disciplinary boundaries and the establishment of professional networks among researchers are highly advantageous for the ESRs, regardless of their career trajectory.
These skills are in high demand, particularly within the rapidly expanding nanomedicine field, so there is a clear need for advanced, multidisciplinary training to support its ongoing development. This strategic investment in training is pivotal for surmounting existing and emerging health challenges, as researchers endeavour to devise innovative solutions transcending the limitations of conventional drug delivery systems and herald a new era of treatment strategies.
The HeatNMof project aims to develop intelligent multifunctional nanocarriers for challenging anticancer drugs. It utilizes biocompatible, highly porous nano-sized Metal-Organic Frameworks (nanoMOFs), integrated with plasmonic and magnetic inorganic nanoparticles. This approach enables specific control of reactions within living entities, like heat-activated drug release, and offers additional properties for imaging and/or hyperthermia therapy.
Project Funding
HeatNMof | 2023® This Project receives funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 860942
Project Partners https://heatnmof.eu/about-us/ Contact Details
Project Coordinator, Eduardo Mota Espacio de Negocios LOOM Tapices Calle de Vandergoten, 1 28014 Madrid (Spain) T: +34 91 548 54 59 E: eduardomota@rtdi.eu W: https://heatnmof.eu
1. Ceballos, M., Cedrún-Morales, M., et al. (2022). Highyield halide-assisted synthesis of metal–organic framework UiO-based nanocarriers. Nanoscale, 14(6789-6801). https://doi.org/10.1039/D1NR08305H
2. Lelouche, S. N. K., & Albentosa-González, L., et al. (2023). Antibacterial Cu or Zn-MOFs Based on the 1,3,5-Tris-(styryl)benzene Tricarboxylate. Nanomaterials, 13(16), 2294. https://doi.org/10.3390/nano13162294
3. Gedikoglu, N., Ostolaza-Paraiso, J., et al. (2024). Isoreticularity in a gallate- based metal–organic framework: Impact of the extension of the ligand on the porosity, stability and adsorption of CO2. Microporous and Mesoporous Materials, 367, 112968. https://doi. org/10.1016/j.micromeso.2023.112968
4. Ceballos, M., Funes-Hernando, S., et al. (2024). SeededGrowth of PCN-224 onto Plasmonic Nanoparticles: Photoactive Microporous Nanocarriers. Small Structures. https://doi.org/10.1002/sstr.202300464
5. Craig, T. M., Ajinkya, A., et al. (2023). Real-time tilt undersampling optimization during electron tomography of beam sensitive samples using golden ratio scanning and RECAST3D. Nanoscale, 15(5391-5402). https://doi. org/10.1039/D2NR07198C
6. Liu, Z., Zimpel, A., et al. (2023). Uptake and intracellular fate of fluorophore labelled metal-organic-framework (MOF) particles. Environment & Health, 1(270–277). https://doi.org/10.1021/envhealth.3c00075
7. Graván, P., Rojas, S., Picchi, D. F., Galisteo-González, F., Horcajada, P., & Marchal, J. A. (2024). Towards a More Efficient Breast Cancer Therapy Using Active Human Cell Membrane-Coated Metal–Organic Frameworks. Nanomaterials, 14(9), 784. https://doi.org/10.3390/nano14090784
Patricia Horcajada
Patricia Horcajada is Head of the Advanced Porous Materials Unit at IMDEA Energía. E: patricia.horcajada@imdea.org
