Enhanced Antibacterial Activity of Vancomycin Loaded on Functionalized Polyketones.

Today, polymeric drug delivery systems (DDS) appear as an interesting solution against bacterial resistance, having great advantages such as low toxicity, biocompatibility, and biodegradability. In this work, two polyketones (PK) have been post-functionalized with sodium taurinate (PKT) or potassium sulfanilate (PKSK) and employed as carriers for Vancomycin against bacterial infections. Modified PKs were easily prepared by the Paal-Knorr reaction and loaded with Vancomycin at a variable pH. All polymers were characterized by FT-IR, DSC, TGA, SEM, and elemental analysis. Antimicrobial activity was tested against Gram-positive Staphylococcus aureus ATCC 25923 and correlated to the different pHs used for its loading (between 2.3 and 8.8). In particular, the minimum inhibitory concentrations achieved with PKT and PKSK loaded with Vancomycin were similar, at 0.23 µg/mL and 0.24 µg/mL, respectively, i.e., six times lower than that with Vancomycin alone. The use of post-functionalized aliphatic polyketones has thus been demonstrated to be a promising way to obtain very efficient polymeric DDS.

Exploring the cellular antioxidant mechanism against cytotoxic silver nanoparticles: a Raman spectroscopic analysis.

Silver nanoparticles (AgNPs) hold great promise for several different applications, from colorimetric sensors to antimicrobial agents. Despite their widespread incorporation in consumer products, limited understanding of the detrimental effects and cellular antioxidant responses associated with AgNPs at sublethal concentrations persists, raising concerns for human and ecological well-being. To address this gap, we synthesized AgNPs of varying sizes and evaluated their cytotoxicity against human dermal fibroblasts (HDF). Our study revealed that toxicity of AgNPs is a time- and size-dependent process, even at low exposure levels. AgNPs exhibited low short-term cytotoxicity but high long-term impact, particularly for the smallest NPs tested. Raman microspectroscopy was employed for in-time investigations of intracellular molecular variations during the first 24 h of exposure to AgNPs of 35 nm. Subtle protein and lipid degradations were detected, but no discernible damage to the DNA was observed. Signals associated with antioxidant proteins, such as superoxide dismutase (SOD), catalase (CAT) and metallothioneins (MTs), increased over time, reflecting the heightened production of these defense agents. Fluorescence microscopy further confirmed the efficacy of overexpressed antioxidant proteins in mitigating ROS formation during short-term exposure to AgNPs. This work provides valuable insights into the molecular changes and remedial strategies within the cellular environment, utilizing Raman microspectroscopy as an advanced analytical technique. These findings offer a novel perspective on the cytotoxicity mechanism of AgNPs, contributing to the development of safer materials and advice on regulatory guidelines for their biomedical applications.

Statistical approaches to Raman imaging: principal component score mapping.

In this research, Raman imaging was employed to map various samples, and the resulting data were analyzed using a suite of automated tools to extract critical information, including intensity and signal-to-noise ratio. The acquired spectra were further processed to identify similarities and investigate patterns using principal component analysis. The objective of this study was to establish guidelines for investigating Raman imaging results, particularly when dealing with large datasets comprising thousands of relatively low-intensity spectra. The overall quality of the results was assessed, and representative locations were determined based on the main Raman bands. While automated software solutions are insufficient for removing baselines and fitting the data, statistical analysis proved to be a powerful tool for extracting valuable information directly from the raw spectral data. This approach enables the extraction of as much information as possible from large arrays of spectral data, even in complex cases where automated software may fall short. The findings of this study contribute to enhancing the analysis and interpretation of Raman imaging results, providing researchers with a robust methodology for extracting meaningful insights from complex datasets, reducing the amount of effort required during data interpretation and analysis.

Ammonia Toxicity and Associated Protein Oxidation: A Single-Cell Surface Enhanced Raman Spectroscopy Study.

Ammonia (NH3) is a commonly used industrial chemical to which exposure at high concentrations can result in severe skin damage. Moreover, high levels of ammonia in the human body can lead to hyperammonemia conditions and enhanced cancer metabolism. In this work, the toxicity mechanism of NH3 has been studied against human dermal fibroblast (HDF) cells using surface-enhanced Raman spectroscopy (SERS). For this purpose, gold nanoparticles of size 50 nm have been prepared and used as probes for Raman signal enhancement, after being internalized inside HDF cells. Following the exposure to ammonia, HDF cells showed a significant variation in the protein ternary structure's signals, demonstrating their denaturation and oxidation process, together with early signs of apoptosis. Meaningful changes were observed especially in the Raman vibrations of sulfur-containing amino acids (cysteine and methionine) together with aromatic residues. Fluorescence microscopy revealed the formation of reactive oxygen and nitrogen species in cells, which confirmed their stressed condition and to whom the causes of protein degradation can be attributed. These findings can provide new insights into the mechanism of ammonia toxicity and protein oxidation at a single-cell level, demonstrating the high potential of the SERS technique in investigating the cellular response to toxic compounds.

In Situ Raman Study of Neurodegenerated Human Neuroblastoma Cells Exposed to Outer-Membrane Vesicles Isolated from Porphyromonas gingivalis.

The aim of this study was to elucidate the chemistry of cellular degeneration in human neuroblastoma cells upon exposure to outer-membrane vesicles (OMVs) produced by Porphyromonas gingivalis (Pg) oral bacteria by monitoring their metabolomic evolution using in situ Raman spectroscopy. Pg-OMVs are a key factor in Alzheimer's disease (AD) pathogenesis, as they act as efficient vectors for the delivery of toxins promoting neuronal damage. However, the chemical mechanisms underlying the direct impact of Pg-OMVs on cell metabolites at the molecular scale still remain conspicuously unclear. A widely used in vitro model employing neuroblastoma SH-SY5Y cells (a sub-line of the SK-N-SH cell line) was spectroscopically analyzed in situ before and 6 h after Pg-OMV contamination. Concurrently, Raman characterizations were also performed on isolated Pg-OMVs, which included phosphorylated dihydroceramide (PDHC) lipids and lipopolysaccharide (LPS), the latter in turn being contaminated with a highly pathogenic class of cysteine proteases, a key factor in neuronal cell degradation. Raman characterizations located lipopolysaccharide fingerprints in the vesicle structure and unveiled so far unproved aspects of the chemistry behind protein degradation induced by Pg-OMV contamination of SH-SY5Y cells. The observed alterations of cells' Raman profiles were then discussed in view of key factors including the formation of amyloid ß (Aß) plaques and hyperphosphorylated Tau neurofibrillary tangles, and the formation of cholesterol agglomerates that exacerbate AD pathologies.

Modification of Amorphous Mesoporous Zirconia Nanoparticles with Bisphosphonic Acids: A Straightforward Approach for Tailoring the Surface Properties of the Nanoparticles.

The use of readily prepared bisphosphonic acids obtained in few steps through a thio-Michael addition of commercially available thiols on tetraethyl vinylidenebisphosphonate enables the straightforward surface modification of amorphous mesoporous zirconia nanoparticles. Simple stirring of the zirconia nanoparticles in a buffered aqueous solution of the proper bisphosphonic acid leads to the surface functionalization of the nanoparticles with different kinds of functional groups, charge and hydrophobic properties. Formation of both chemisorbed and physisorbed layers of the bisphosphonic acid take place, observing after extensive washing a grafting density of 1.1 molecules/nm2 with negligible release in neutral or acidic pH conditions, demonstrating stronger loading compared to monophosphonate derivatives. The modified nanoparticles were characterized by IR, XPS, ζ-potential analysis to investigate the loading of the bisphosphonic acid, FE-SEM to investigate the size and morphologies of the nanoparticles and 31 P and 1 H MAS NMR to investigate the coordination motif of the phosphonate units on the surface. All these analytical techniques demonstrated the strong affinity of the bisphosphonic moiety for the Zr(IV) metal centers. The functionalization with bisphosphonic acids represents a straightforward covalent approach for tailoring the superficial properties of zirconia nanoparticles, much straightforward compared the classic use of trisalkoxysilane or trichlorosilane reagents typically employed for the functionalization of silica and metal oxide nanoparticles. Extension of the use of bisphosphonates to other metal oxide nanoparticles is advisable.

Synthesis and Antimicrobial Evaluation of Bis-morpholine Triazine Quaternary Ammonium Salts.

Efficient, environmentally and economically sustainable, and nontoxic antibacterial products are of global relevance in the fight against microorganism contamination. In this work, an easy and straightforward method for the synthesis of bis-morpholino triazine quaternary ammonium salts (bis-mTQAS) is reported, starting from 2,4,6-trichloro-1,3,5-triazine or 2,4-dichloro-6-methoxy-1,3,5-triazine and various N-alkylmorpholines. Bis-mTQAS were tested as antimicrobials against Gram-negative and Gram-positive bacterial strains. The best-performing bis-mTQAS were found to achieve total disinfection against Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922 at 50 and 400 µg/mL, respectively. Distinctively, bis-mTQAS with the highest antimicrobial efficiency had lowest cytotoxicity.

Confined-Melting-Assisted Synthesis of Bismuth Silicate Glass-Ceramic Nanoparticles: Formation and Optical Thermometry Investigation.

Bismuth-based (nano)materials have been attracting increasing interest due to appealing properties such as high refractive indexes, intrinsic opacity, and structural distortions due to the stereochemistry of 6s2 lone pair electrons of Bi3+. However, the control over specific phases and strategies able to stabilize uniform bismuth-based (nano)materials is still a challenge. In this study, we employed the ability of bismuth to lower the melting point of silica to introduce a new synthetic approach able to confine the growth of bismuth-oxide-based materials into nanostructures. Combining in situ temperature-dependent synchrotron radiation X-ray powder diffraction (XRPD) with high-resolution transmission electron microscopy (HR-TEM) analyses, we demonstrate the evolution of a confined Bi2O3-SiO2 nanosystem from Bi2SiO5 to Bi4Si3O12 through a melting process. The silica shell acts as both a nanoreactor and a silicon source for the stabilization of bismuth silicate glass-ceramic nanocrystals keeping the original spherical shape. The exciton peak of Bi2SiO5 is measured for the first time allowing the estimation of its real energy gap. Moreover, based on a detailed spectroscopic investigation, we discuss the potential and the limitations of Nd3+-activated bismuth silicate systems as ratiometric thermometers. The synthetic strategy introduced here could be further explored to stabilize other bismuth-oxide-based materials, opening the way toward the growth of well-defined glass-ceramic nanoparticles.

Recellularized Colorectal Cancer Patient-derived Scaffolds as in vitro Pre-clinical 3D Model for Drug Screening.

Colorectal cancer (CRC) shows highly ineffective therapeutic management. An urgent unmet need is the random assignment to adjuvant chemotherapy of high-risk stage II and stage III CRC patients without any predictive factor of efficacy. In the field of drug discovery, a critical step is the preclinical evaluation of drug cytotoxicity, efficacy, and efficiency. We proposed a patient-derived 3D preclinical model for drug evaluation that could mimic in vitro the patient's disease. Surgically resected CRC tissue and adjacent healthy colon mucosa were decellularized by a detergent-enzymatic treatment. Scaffolds were recellularized with HT29 and HCT116 cells. Qualitative and quantitative characterization of matched recellularized samples were evaluated through histology, immunofluorescences, scanning electron microscopy, and DNA amount quantification. A chemosensitivity test was performed using an increasing concentration of 5-fluorouracil (5FU). In vivo studies were carried out using zebrafish (Danio rerio) animal model. Permeability test and drug absorption were also determined. The decellularization protocol allowed the preservation of the original structure and ultrastructure. Five days after recellularization with HT29 and HCT116 cell lines, the 3D CRC model exhibited reduced sensitivity to 5FU treatments compared with conventional 2D cultures. Calculated the half maximal inhibitory concentration (IC50) for HT29 treated with 5FU resulted in 11.5 µM in 3D and 1.3 µM in 2D, and for HCT116, 9.87 µM in 3D and 1.7 µM in 2D. In xenograft experiments, HT29 extravasation was detected after 4 days post-injection, and we obtained a 5FU IC50 fully comparable to that observed in the 3D CRC model. Using confocal microscopy, we demonstrated that the drug diffused through the repopulated 3D CRC scaffolds and co-localized with the cell nuclei. The bioengineered CRC 3D model could be a reliable preclinical patient-specific platform to bridge the gap between in vitro and in vivo drug testing assays and provide effective cancer treatment.

Bismuth titanate-based UV filters embedded mesoporous silica nanoparticles: Role of bismuth concentration in the self-sealing process.

The development of new safe inorganic UV filters to effectively protect the skin from ultraviolet (UV) radiation effects is an emerging issue. Bismuth titanate-based UV filters embedded into mesoporous silica nanoparticles (MSN) represent a new class of inorganic sunscreens, with excellent UVA and UVB shielding properties. In addition, the presence of bismuth ions promotes a self-sealing process, allowing (i) the entrapment of the active phases in the deepest core of the system and (ii) the formation of an external glassy silica layer with a consequent suppression of the photocatalytic activity. In this work, aimed at studying in detail the self-sealing mechanism and accessing the role of bismuth ions in the formation of the system, a series of samples impregnated with a different amount of bismuth were investigated. The self-sealing process already occurs at the lowest content of bismuth and the mechanism is demonstrated to be triggered by the ability of Bi to work as a low-melting point agent for silica. Finally, a sunscreen formulation containing the new UV filter was prepared and the Sun Protection Factor (SPF), the pH and the viscosity were measured, demonstrating the potential of the proposed material for large-scale applications.

Bi2SiO5@g-SiO2 upconverting nanoparticles: a bismuth-driven core-shell self-assembly mechanism.

Core-shell systems have attracted increasing interest among the research community in recent years due to their unique properties and structural features, and the development of new synthetic strategies is still a challenge. In this work, we have investigated lanthanide-doped Bi2SiO5 nanocrystal formation inside mesoporous silica nanoparticles (MSNs). The role of both synthesis temperature and concentration of the bismuth precursor impregnated into the MSNs is discussed, showing an unprecedented strategy for the simultaneous stabilization of a crystalline core and a glassy shell. Temperature dependent synchrotron radiation X-ray powder diffraction (SR-XRPD) and high resolution transmission electron microscopy (HR-TEM) analyses allow one to follow the crystalline core growth. A mechanism for the formation of a Bi2SiO5@g-SiO2 core-shell nanosystem is proposed. In addition, the easy tunability of the color output of the upconverting system is demonstrated by means of suitable doping lanthanide ions with potential applications in several fields.

Ag-Sensitized Yb3+ Emission in Glass-Ceramics.

Rare earth doped materials play a very important role in the development of many photonic devices, such as optical amplifiers and lasers, frequency converters, solar concentrators, up to quantum information storage devices. Among the rare earth ions, ytterbium is certainly one of the most frequently investigated and employed. The absorption and emission properties of Yb3+ ions are related to transitions between the two energy levels ²F7/2 (ground state) and ²F5/2 (excited state), involving photon energies around 1.26 eV (980 nm). Therefore, Yb3+ cannot directly absorb UV or visible light, and it is often used in combination with other rare earth ions like Pr3+, Tm3+, and Tb3+, which act as energy transfer centres. Nevertheless, even in those co-doped materials, the absorption bandwidth can be limited, and the cross section is small. In this paper, we report a broadband and efficient energy transfer process between Ag dimers/multimers and Yb3+ ions, which results in a strong PL emission around 980 nm under UV light excitation. Silica-zirconia (70% SiO2-30% ZrO2) glass-ceramic films doped by 4 mol.% Yb3+ ions and an additional 5 mol.% of Na2O were prepared by sol-gel synthesis followed by a thermal annealing at 1000 °C. Ag introduction was then obtained by ion-exchange in a molten salt bath and the samples were subsequently annealed in air at 430 °C to induce the migration and aggregation of the metal. The structural, compositional, and optical properties were investigated, providing evidence for efficient broadband sensitization of the rare earth ions by energy transfer from Ag dimers/multimers, which could have important applications in different fields, such as PV solar cells and light-emitting near-infrared (NIR) devices.

Carbon Dots from Sugars and Ascorbic Acid: Role of the Precursors on Morphology, Properties, Toxicity, and Drug Uptake.

There is the need for reproducible, simple, high-yielding synthetic protocols aimed at obtaining carbon dots (CDs) with controlled fluorescence, photothermal and photochemical behavior, surface properties, biocompatibility, tumor targeting ability, drug absorption biodistribution, and tumor uptake. This Letter describes a systematic study on the effect of glucose, fructose, and ascorbic acid as starting materials for the preparation of highly luminescent CDs, characterized by a blue emission. Their composition and morphology are investigated by titration of OH surface groups, spectroscopic techniques, and high-resolution transmission electron microscopy (HR-TEM), and their toxicity was tested toward HeLa cells. CDs made using fructose were toxic, while those made from glucose and ascorbic acid showed good biocompatibility. The reproducible and simple synthetic procedure yields luminescent biomass-derived CDs for combined cancer therapy and diagnostics. Their doxorubicin (DOX) drug uptake was measured by spectrofluorimetry, indicating a crucial role of the morphologies of the CDs in controlling DOX loading. The glucose derived CDs showed up to 28% w/w of DOX loading.

Inorganic Nanoparticles for Cancer Therapy: A Transition from Lab to Clinic.

BACKGROUND: Inorganic nanoparticles (NPs) including those derived from metals (e.g., gold, silver), semiconductors (e.g., quantum dots), carbon dots, carbon nanotubes, or oxides (e.g., iron oxide), have been deeply investigated recently for diagnostic and therapeutic purposes in oncology. Compared to organic nanomaterials, inorganic NPs have several advantages and unique characteristics for better imaging and drug delivery. Still, only a limited number of inorganic NPs are translated into clinical practice. METHOD: In this review, we discuss the progression of inorganic NPs for cancer therapy and imaging, focusing our attention on opportunities, limitations and challenges for the main constituting nanomaterials, including metallic and magnetic NPs. In particular, the pre-clinical and clinical trials from the bench toward the clinic are here investigated. RESULTS: Over the last few decades, the development of wide range of NPs with the ability to tune size, composition and functionality, has provided an excellent resource for nanomedicine. Inorganic NPs provide a great opportunity as drug carriers, due to the easy modification of targeting molecules, the control of drug release by different stimuli, and the effective delivery to target sites, thus resulting in having an improved therapeutic efficacy and in reducing side effects. Inorganic NPs are investigated in preclinical and clinical studies for the detection, diagnosis and treatment of many diseases. The stability of inorganic NPs offers a potential advantage over the traditional delivery methods. Inorganic NPs could enhance and improve current imaging and diagnostic techniques, such as MRI or PET. Even though, they have not yet been approved for drug delivery applications, their ability to respond to external stimuli is now widely investigated in clinic. CONCLUSION: The successful translation of inorganic NPs to the clinic requires the development of a simple, safe, cost-effective, ecofriendly mode of synthesis, and a better understanding of the safety mechanisms, biodistribution and the pharmacokinetics of NPs. However, more attention should be given to concerns on long-term toxicity, carcinogenesis, immunogenicity, inflammation and tissue damage. Although, some inorganic NPs, which were apparently promising in the preclinical phase, were found not to be successful when translated to the clinic, several encouraging NPs are currently being developed for treatment and cancer care and for a wide variety of other diseases.

Bottom-up synthesis of carbon nanoparticles with higher doxorubicin efficacy.

Nanomedicine requires intelligent and non-toxic nanomaterials for real clinical applications. Carbon materials possess interesting properties but with some limitations due to toxic effects. Interest in carbon nanoparticles (CNPs) is increasing because they are considered green materials with tunable optical properties, overcoming the problem of toxicity associated with quantum dots or nanocrystals, and can be utilized as smart drug delivery systems. Using black tea as a raw material, we synthesized CNPs with a narrow size distribution, tunable optical properties covering visible to deep red absorption, non-toxicity and easy synthesis for large-scale production. We utilized these CNPs to label subcellular structures such as exosomes. More importantly, these new CNPs can escape lysosomal sequestration and rapidly distribute themselves in the cytoplasm to release doxorubicin (doxo) with better efficacy than the free drug. The release of doxo from CNPs was optimal at low pH, similar to the tumour microenvironment. These CNPs were non-toxic in mice and reduced the tumour burden when loaded with doxo due to an improved pharmacokinetics profile. In summary, we created a new delivery system that is potentially useful for improving cancer treatments and opening a new window for tagging microvesicles utilized in liquid biopsies.

Formation and Controlled Growth of Bismuth Titanate Phases into Mesoporous Silica Nanoparticles: An Efficient Self-Sealing Nanosystem for UV Filtering in Cosmetic Formulation.

The application of nanosized inorganic UV filters in cosmetic field is limited by their high photocatalytic properties that could induce the degradation or dangerous transformation of the organic molecules in sunscreen formulations. To overcome this problem and simultaneously enlarge the window of filter's absorption, we propose the growth of bismuth titanates BixTiyOz into mesoporous silica nanoparticles (MSN). We investigated the chemical-physical properties by means of XRPD, TEM, UV-vis spectroscopy, N2 physisorption, XPS, and SF-ICP-MS analysis, while the influence on the environment was evaluated through photocatalytic tests. The growing process of this new nanosystem is discussed underlining the key role of the Bi3+ ion that, acting as a low-melting point agent for the silica framework, led to a self-sealing mechanism. The excellent UV shielding properties combined with a radical suppression of the photocatalytic activity make the proposed nanosystem a perfect candidate for the development of the next generation nanomaterials for sunscreen formulations.

Towards a Rational Design of a Continuous-Flow Method for the Acetalization of Crude Glycerol: Scope and Limitations of Commercial Amberlyst 36 and AlF3·3H2O as Model Catalysts.

The acetalization of six different types of glycerol including pure, wet, and crude-like grade compounds of compositions simulating those of crude glycerols produced by the biodiesel manufacture, was carried out with two model ketones such as acetone and 2-butanone. The reaction was investigated under continuous-flow (CF) conditions through a comparative analysis of an already known acetalization catalyst such as Amberlyst 36 (A36), and aluminum fluoride three hydrate (AlF3·3H2O, AF) whose use was never previously reported for the synthesis of acetals. At 10 bar and 25 °C, A36 was a highly active catalyst allowing good-to-excellent conversion (85%-97%) and selectivity (99%) when either pure or wet glycerol was used as a reagent. This catalyst however, proved unsuitable for the CF acetalization of crude-like glycerol (CG) since it severely and irreversibly deactivated in a few hours by the presence of low amounts of NaCl (2.5 wt %) which is a typical inorganic impurity of raw glycerol from the biorefinery. Higher temperature and pressure (up to 100 °C and 30 bar) were not successful to improve the outcome. By contrast, at 10 bar and 100 °C, AF catalyzed the acetalization of CG with both acetone and 2-butanone, yielding stable conversion and productivity up to 78% and 5.6 h(-1), respectively. A XRD analysis of fresh and used catalysts proved that the active phase was a solid solution (SS) of formula Al2[F1-x(OH)x]6(H2O)y present as a component of the investigated commercial AF sample. A hypothesis to explain the role of such SS phase was then formulated based on the Brønsted acidity of OH groups of the solid framework. Overall, the AF catalyst allowed not only a straightforward upgrading of CG to acetals, but also a more cost-efficient protocol avoiding the expensive refining of raw glycerol itself.

Determining europium compositional fluctuations in partially stabilized zirconia nanopowders: a non-line-broadening-based method.

A method is reported for assessing the compositional fluctuations in a ceramic sample, based only on the determination of the crystalline lattice parameters. Pure tetragonal phase partially stabilized zirconia powders are synthesized through the co-precipitation method by incorporating 4% Eu(3+). The powder is subjected to compression cycles to promote the tetragonal-to-monoclinic transformation. The Rietveld analysis of the X-ray powder diffraction patterns, recorded after each compression cycle, gives information about the lattice parameters and monoclinic phase content. The determination of europium content in the residual tetragonal phase is accomplished considering the unit cell volume of t-ZrO2 using Vegard's law. Using this information the compositional fluctuations over the sample were determined by considering two possible distributions of lanthanide ion content in the powders: a Gaussian and a Log-normal one. It was found that the Gaussian distribution better fits the experimental data. It was eventually demonstrated that these results are physically meaningful.

Biocompatible tailored zirconia mesoporous nanoparticles with high surface area for theranostic applications.

Nanocarriers as theranostic agents are under the spotlight in modern nanomedicine, and mesoporous nanomaterials represent a class of devices of major interest. Zirconia is biocompatible, inert with good mechanical and thermal properties for in vivo biomedical applications. Although a few examples of zirconia nanoparticles have been described, a major limitation was the low surface area, which is fundamental for payload transport. Here, a simple and highly efficient method is described for the synthesis of spherical mesoporous zirconia nanoparticles (MZNs) with a high surface area through a neutral surfactant-assisted sol-gel method. The combination of alkali halides and vacuum extraction allowed stabilization of the shape and size of MZNs and to avoid porous network failure, respectively. In comparison to published synthesis procedures, a high surface area has been obtained. Biological experiments demonstrated that MZNs were biocompatible, cell permeable and degradable providing a proof of concept for theranostic applications. A comparison with the properties of mesoporous silica nanoparticles has also been performed.