The HeatNMOF project, coordinated by IMDEA Energy, was focused on developing multifunctional nanocomposite materials by combining the highly porous and versatile structure of biocompatible nano-Metal-Organic Frameworks (nanoMOFs) with plasmonic and magnetic inorganic nanoparticles (iNPs). These composites are designed to offer exceptional drug payloads with controlled release capabilities while also providing specific control of reactions within living organisms, such as drug delivery triggered by photothermal or alternating magnetic field (AMF) heating. During the last 5 years, consortium efforts have been dedicated to synthesizing MOFs and MOF composites with a focus on controlling specific properties such as size, porosity, functionality, and their applications in drug delivery, catalysis, and antibacterial activity. Recent research emphasizes several methods for synthesizing nanosized MOFs and their composites. For instance, nanosized UiO-66 MOFs were synthesized using halide ions to control morphology and size, achieving high crystallinity and stable colloidal properties, which are crucial parameters for effective drug delivery (Nanoscale, 2022, 14, 6789). Another study introduces novel antibacterial MOFs, IEF-23 and IEF-24, which are solvothermally synthesized and show promising activity against Staphylococcus epidermidis and Escherichia coli (Nanomaterials, 2023, 16, 2294), emphasizing the role of tricarboxylate linkers and metal cations in therapeutic applications. The concept of isoreticularity is explored in another study (Microporous Mesoporous Mater., 2024, 367, 112968), enhancing the surface area and pore volume of a gallate-ligand-based MOF, demonstrating the importance of structural modifications to improve drug loading and release. Additionally, a highly porous Hf-tetracarboxylate porphyrin-based MOF was synthesized using a microwave-assisted method, highlighting the efficiency and scalability of this approach for catalytic applications (Mater. Adv. Today, 2023, 19, 100390). Moreover, a study on metal-sulfur bonded MOFs with Fe(III) expands the scope of S-based MOFs, focusing on electronic properties and their potential in controlled drug release (J. Mater. Chem. A., 2023, 11, 23909).

Some research groups of the consortium have focused on integrating MOFs with iNPs to develop new-generation composite materials with outstanding drug encapsulation and externally (light and/or AMF) controlled drug delivery capability. Two main strategies have been employed, particularly involving plasmonic NPs. First, Au NPs (Chemistry-a European Journal, 2024, 30, e202400442) and PtAg nanoclusters (Nanoselect 22021, 2, 758; Small, 2023, 19, 2206772) were grown within the porosity of MIL-88B-NH₂ and ZIF-8 showing high catalytic activity and potential applications in energy and drug delivery. Secondly, a novel approach involves the creation of microporous plasmonic nanocomposites by using gold bipyramids as seeds for the growth of MOFs like PCN-224 (Small structures, 2024, 5, 5, 2300464). The control over the MOF shell thickness impacts the thermoplasmonic properties, enhancing thermal confinement and supporting applications in intracellular drug release and photodynamic therapy.

Advanced characterization techniques are critical in these studies, with Electron Tomography being widely used for 3D structural analysis of these nanomaterials, providing in-depth insights into the complex architectures of MOF@iNPs composites (Nanoscale, 2023, 15, 5391).

For instance, a gold nanostar core in a polymer-stabilized ZIF-8 MOF shell, enabling NIR-driven photothermal cyclization inside living cells for the spatial and temporal activation of prodrugs, was visualized through fluorescence microscopy (ACS Nano, 2021, 15, 10, 16924). Another light-responsive nanoscale MOF composite enabled spatiotemporal targeted drug delivery, which was demonstrated through studies in 2D and 3D cell culture (Small Science, 2024, 2400088). The fate of MOF composites in cells was also studied in details by monitoring the uptake of Zr-based MOF labeled with organic fluorophores in HeLa cells, revealing that nanoparticle clearance is driven more by cell proliferation than exocytosis, which has implications for MOF-based drug delivery applications (Environment & Health, 2023, 1, 270). Moreover, it was demonstrated that coating MIL-100(Fe) nanoparticles with cell membranes from a human triple-negative breast cancer (TNBC) cell line improves their stability, cellular uptake, and cytotoxicity, suggesting their potential as targeted therapies for TNBC (Nanomaterials, 2024, 14, 784).

Another potential therapeutic application was found for nanoMOFs. Particularly, the mesoporous iron(III)-trimesate MIL-100 serves as anti-COVID-19 agent, given its significant antiviral effects and high biocompatibility (ACS Applied Materials and Interfaces, 2024, 16, 25, 32118). More results will be also published in the direction of validations of different materials developed by us as drug carriers for chemotherapeutic agents with toxic effects often occurring under the magnetic activation of magnetic-MOF composites, but at exploiting local heat effects rather than direct heat damage. This will enable to reduce the requested dose of MOF-composite to achieve therapeutic effects.

Overall, advanced characterizations combined with the innovative synthetic methods underscore the versatility and adaptability of MOFs in various high-impact applications, from therapy (e.g. cancer, infection) to catalysis.