Nanoscaled metal-organic frameworks: charting a transformative path for cancer therapeutics and beyond.

Through this inspirational note, we would like to highlight the potential of nanoscaled metal-organic frameworks within the biomedical field. The unique properties of these materials that make them promising candidates for new nanomedicines are assessed here as well as the progression reached so far for combinational cancer therapies and theranostic, along with its most recent advances in nanomedicine. Finally, the perspective and challenges of these materials within this field is discussed.

Nanocomposites Based on Magnetic Nanoparticles and Metal-Organic Frameworks for Therapy, Diagnosis, and Theragnostics.

In the last two decades, metal-organic frameworks (MOFs) with highly tunable structure and porosity, have emerged as drug nanocarriers in the biomedical field. In particular, nanoscaled MOFs (nanoMOFs) have been widely investigated because of their potential biocompatibility, high drug loadings, and progressive release. To enhance their properties, MOFs have been combined with magnetic nanoparticles (MNPs) to form magnetic nanocomposites (MNP@MOF) with additional functionalities. Due to the magnetic properties of the MNPs, their presence in the nanosystems enables potential combinatorial magnetic targeted therapy and diagnosis. In this Review, we analyze the four main synthetic strategies currently employed for the fabrication of MNP@MOF nanocomposites, namely, mixing, in situ formation of MNPs in presynthesized MOF, in situ formation of MOFs in the presence of MNPs, and layer-by-layer methods. Additionally, we discuss the current progress in bioapplications, focusing on drug delivery systems (DDSs), magnetic resonance imaging (MRI), magnetic hyperthermia (MHT), and theragnostic systems. Overall, we provide a comprehensive overview of the recent advances in the development and bioapplications of MNP@MOF nanocomposites, highlighting their potential for future biomedical applications with a critical analysis of the challenges and limitations of these nanocomposites in terms of their synthesis, characterization, biocompatibility, and applicability.

AuNP/MIL-88B-NH2 Nanocomposite for the Valorization of Nitroarene by Green Catalytic Hydrogenation.

The efficiency of a catalytic process is assessed based on conversion, yield, and time effectiveness. However, these parameters are insufficient for evaluating environmentally sustainable research. As the world is urged to shift towards green catalysis, additional factors such as reaction media, raw material availability, sustainability, waste minimization and catalyst biosafety, need to be considered to accurately determine the efficacy and sustainability of the process. By combining the high porosity and versatility of metal organic frameworks (MOFs) and the activity of gold nanoparticles (AuNPs), efficient, cyclable and biosafe composite catalysts can be achieved. Thus, a composite based on AuNPs and the nanometric flexible porous iron(III) aminoterephthalate MIL-88B-NH2 was successfully synthesized and fully characterized. This nanocomposite was tested as catalyst in the reduction of nitroarenes, which were identified as anthropogenic water pollutants, reaching cyclable high conversion rates at short times for different nitroarenes. Both synthesis and catalytic reactions were performed using green conditions, and even further tested in a time-optimizing one-pot synthesis and catalysis experiment. The sustainability and environmental impact of the catalytic conditions were assessed by green metrics. Thus, this study provides an easily implementable synthesis, and efficient catalysis, while minimizing the environmental and health impact of the process.

Antibacterial Cu or Zn-MOFs Based on the 1,3,5-Tris-(styryl)benzene Tricarboxylate.

Metal-organic frameworks (MOFs) are highly versatile materials. Here, two novel MOFs, branded as IEF-23 and IEF-24 and based on an antibacterial tricarboxylate linker and zinc or copper cations, and holding antibacterial properties, are presented. The materials were synthesized by the solvothermal route and fully characterized. The antibacterial activity of IEF-23 and IEF-24 was investigated against Staphylococcus epidermidis and Escherichia coli via the agar diffusion method. These bacteria are some of the most broadly propagated pathogens and are more prone to the development of antibacterial resistance. As such, they represent an archetype to evaluate the efficiency of novel antibacterial treatments. MOFs were active against both strains, exhibiting higher activity against Staphylococcus epidermidis. Thus, the potential of the developed MOFs as antibacterial agents was proved.

Advances in plasmonic-based MOF composites, their bio-applications, and perspectives in this field.

INTRODUCTION: Nanomaterials have been used for bio-applications since the late twentieth century. In an attempt to tailor and optimize their properties, and by extension their efficiency, composites have attracted considerable attention. In this regard, recent studies on plasmonic nanoparticles and metal-organic framework (NP@MOF) composites suggest that these materials show great promise in this field. AREAS COVERED: This review focused on the more recent scientific advances in the synthetic strategies to optimize plasmonic MOF nanocomposites currently available, as well as their bio-application, particularly as biosensors and in therapy. EXPERT OPINION: Plasmonic MOF nanocomposites have shown a great potential as they combine the properties of both materials with proven efficiency in bio-application. On the one hand, nanoMOFs have proven their potential particularly as drug nanocarriers, owing to their exceptional porosity and tunability. On the other hand, plasmonic nanoparticles have been an asset for imaging and phototherapy. Different strategies have been reported to develop these nanocomposites, mainly including core-shell, encapsulation, and in situ reduction. In addition, advanced composite structures should be considered, such as mixed metal nanoparticles, hollow structures, or the combination of several approaches. Specifically, plasmonic MOF nanocomposites prove to be attractive stimuli-responsive drug delivery systems, phototherapeutic agents, and highly sensitive biosensors. [Figure: see text].

Galvanic Replacement as a Synthetic Tool for the Construction of Anisotropic Magnetoplasmonic Nanocomposites with Synergistic Phototransducing and Magnetic Properties.

Magnetoplasmonic nanomaterials, which combine light and magnetic field responsiveness in an advantageous manner, are attractive candidates for bio-nanoapplications. However, the synthetic access to such hybrid particles has been limited by the incompatibility of the iron- and gold-based lattices. In this work, we provide the first insights into a new synthetic strategy for developing magnetoplasmonic anisotropic nanocomposites with prominent phototransducing properties. In our approach, magnetic nanocubes based on an alloy of iron oxide, zinc, and silver were constructed. In a key second stage, the galvanic replacement of silver with gold atoms yielded satellite-like magnetoplasmonic anisotropic structures. Superior magnetic and photoconverting properties were observed for the novel magnetoplasmonic nanocomposites when compared with the pure parent structures. Moreover, the synergy between the magnetic and optical stimuli was examined, showing shape-dependent contributions in the magnetization experiments. More importantly, an excellent cell ablation capability upon laser irradiation was observed for the magnetoplasmonic nanocomposites compared to the pure magnetic or plasmonic controls. Further demonstration of these novel theragnostic agents as MRI contrast agents is also reported even during the light-irradiation event. Thus, the described particles showed promising properties for bioapplications emerging from the novel synthetic methodology.

Revealing the NIR-triggered chemotherapy therapeutic window of magnetic and thermoresponsive nanogels.

The combination of magnetic nanoparticles and thermoresponsive nanogels represents an appealing strategy for the development of theranostic probes. These hybrid nanocarriers present several advantages such as outstanding properties for guided therapy, magnetic resonance imaging, and triggered release of encapsulated cargoes. Most magnetic thermoresponsive nanogels are built with strategies that comprise a physical interaction of particles with the polymeric network or the covalent attachment of a single particle to the linear polymer. Herein, we report a facile synthetic approach for the synthesis of magnetic and thermoresponsive nanogels that allows the controlled incorporation of multiple superparamagnetic inorganic cores as covalent cross-linkers. An ultrasonication-assisted precipitation-polymerization afforded nanogels with sizes in the nanometric range and similar magnetization and light transduction properties compared to the discrete magnetic nanoparticles. The theranostic capability of these nanocarriers was further investigated both in vitro and in vivo. In vivo experiments demonstrated the capacity of these materials as nanocarriers for near-infrared (NIR) triggered chemotherapy and highlighted the relevance of the correct concentration/dose in this antitumoral modality to achieve a superior therapeutic efficacy.

Dual-responsive nanogels based on oligo(ethylene glycol) methacrylates and acidic co-monomers.

Ethylene glycol-based nanogels (NGs) have demonstrated their potential for the development of next-generation formulations for biomedical applications due to their interesting properties. In this work, monodispersed NGs based on oligo(ethylene glycol) methacrylates (OEG) were synthesized through free radical precipitation/dispersion polymerization assisted by ultrasonication. Di(ethylene glycol)methyl ether methacrylate (DEGMA) and oligo(ethylene glycol) methacrylate (OEGMA; Mn 475 g mol-1) were used as the main monomers, acrylic acid (AA) or itaconic acid (IA) as co-monomers (OEG-co-AA and OEG-co-IA, respectively) and tetraethylene glycol dimethacrylate (TEGDMA) as crosslinker. The physicochemical properties of OEG-co-AA and OEG-co-IA NGs were studied including hydrodynamic diameter, poly-dispersity index, zeta potential and pH/temperature responsiveness. Samples with 4 mol% of both AA and IA showed nanometric sizes. Regarding their thermo-responsiveness, unexpected differences between NGs with AA or with IA were observed. Besides, NGs did not impair the cell viability of a breast tumour cell line even when high concentrations were added to the culture medium. The properties of the synthetized NGs showed that either NGs with 4% AA or with 4% IA are outstanding candidates for biomedical applications.

Optimizing Circulating Tumor Cells' Capture Efficiency of Magnetic Nanogels by Transferrin Decoration.

Magnetic nanogels (MNGs) are designed to have all the required features for their use as highly efficient trapping materials in the challenging task of selectively capturing circulating tumor cells (CTCs) from the bloodstream. Advantageously, the discrimination of CTCs from hematological cells, which is a key factor in the capturing process, can be optimized by finely tuning the polymers used to link the targeting moiety to the MNG. We describe herein the relationship between the capturing efficiency of CTCs with overexpressed transferrin receptors and the different strategies on the polymer used as linker to decorate these MNGs with transferrin (Tf). Heterobifunctional polyethylene glycol (PEG) linkers with different molecular weights were coupled to Tf in different ratios. Optimal values over 80% CTC capture efficiency were obtained when 3 PEG linkers with a length of 8 ethylene glycol (EG) units were used, which reveals the important role of the linker in the design of a CTC-sorting system.

Design, Synthesis and Architectures of Hybrid Nanomaterials for Therapy and Diagnosis Applications.

Hybrid nanomaterials based on inorganic nanoparticles and polymers are highly interesting structures since they combine synergistically the advantageous physical-chemical properties of both inorganic and polymeric components, providing superior functionality to the final material. These unique properties motivate the intensive study of these materials from a multidisciplinary view with the aim of finding novel applications in technological and biomedical fields. Choosing a specific synthetic methodology that allows for control over the surface composition and its architecture, enables not only the examination of the structure/property relationships, but, more importantly, the design of more efficient nanodevices for therapy and diagnosis in nanomedicine. The current review categorizes hybrid nanomaterials into three types of architectures: core-brush, hybrid nanogels, and core-shell. We focus on the analysis of the synthetic approaches that lead to the formation of each type of architecture. Furthermore, most recent advances in therapy and diagnosis applications and some inherent challenges of these materials are herein reviewed.

Transferrin Decorated Thermoresponsive Nanogels as Magnetic Trap Devices for Circulating Tumor Cells.

A rational design of magnetic capturing nanodevices, based on a specific interaction with circulating tumor cells (CTCs), can advance the capturing efficiency and initiate the development of modern smart nanoformulations for rapid isolation and detection of these CTCs from the bloodstream. Therefore, the development and evaluation of magnetic nanogels (MNGs) based on magnetic nanoparticles and linear thermoresponsive polyglycerol for the capturing of CTCs with overexpressed transferrin (Tf(+) ) receptors has been presented in this study. The MNGs are synthesized using a strain-promoted "click" approach which has allowed the in situ surface decoration with Tf-polyethylene glycol (PEG) ligands of three different PEG chain lengths as targeting ligands. An optimal value of around 30% of cells captures is achieved with a linker of eight ethylene glycol units. This study shows the potential of MNGs for the capture of CTCs and the necessity of precise control over the linkage of the targeting moiety to the capturing device.