Confinement and Polarity Effects on the Peptide Packing Density on Mesoporous Silica Nanoparticles.

The adsorption of cationic peptide JM21 onto different mesoporous silica nanoparticles (MSNs) from an aqueous solution was studied as a function of pH. In agreement with the literature, the highest loading degrees could be achieved at pH close to the isoelectric point of the peptide where the peptide-peptide repulsion is minimum. However, mesopore size, mesopore geometry, and surface polarity all had an influence on the peptide adsorption in terms of both affinity and maximum loading at a given pH. This adsorption behavior could largely be explained by a combination of pH-dependent electrostatic interactions and confinement effects. It is demonstrated that hydrophobic interactions enhance the degree of peptide adsorption under pH conditions where the electrostatic attraction was absent in the case of mesoporous organosilica nanoparticles (MONs). The lower surface concentration of silanol groups for MON led to a lower level of peptide adsorption under optimum pH conditions compared to all-silica particles. Finally, the study confirmed the protective role of MSNs in preserving the biological activity of JM#21 against enzymatic degradation, even for large-pore MSNs, emphasizing their potential as nanocarriers for therapeutic peptides. By integrating experimental findings with theoretical modeling, this research elucidates the complex interplay of factors that influence peptide-silica interactions, providing vital insights for optimizing peptide loading and stabilization in biomedical applications.

Surface functionalization affects the retention and bio-distribution of orally administered mesoporous silica nanoparticles in a colitis mouse model.

Besides the many advantages of oral drug administration, challenges like premature drug degradation and limited bioavailability in the gastro-intestinal tract (GIT) remain. A prolonged residence time in the GIT is beneficial for enhancing the therapeutic outcome when treating diseases associated with an increased intestinal clearance rate, like inflammatory bowel disease (IBD). In this study, we synthesized rod-shaped mesoporous silica nanoparticles (MSNs) functionalized with polyethylene glycol (PEG) or hyaluronic acid (HA) and investigated their bio-distribution upon oral administration in vivo. The negatively charged, non-toxic particles showed different accumulation behavior over time in healthy mice and in mice with dextran sulfate sodium (DSS)-induced intestinal inflammation. PEGylated particles were shown to accumulate in the lower intestinal tract of healthy animals, whereas inflammation promoted retention of HA-functionalized particles in this area. Overall systemic absorption was low. However, some particles were detected in organs of mice with DSS-induced colitis, especially in the case of MSN-PEG. The in vivo findings were connected to surface chemistry-related differences in particle adhesion on Caco-2/Raji and mucus-producing Caco-2/Raji/HT29 cell co-culture epithelial models in vitro. While the particle adhesion behavior in vivo was mirrored in the in vitro results, this was not the case for the resorption results, suggesting that the in vitro model does not fully reflect the erosion of the inflamed epithelial tissue. Overall, our study demonstrates the possibility to modulate accumulation and retention of MSNs in the GIT of mice with and without inflammation through surface functionalization, which has important implications for the formulation of nanoparticle-based delivery systems for oral delivery applications.

Silica nanoparticles: A review of their safety and current strategies to overcome biological barriers.

Silica nanoparticles (SNP) have gained tremendous attention in the recent decades. They have been used in many different biomedical fields including diagnosis, biosensing and drug delivery. Medical uses of SNP for anti-cancer, anti-microbial and theranostic applications are especially prominent due to their exceptional performance to deliver many different small molecules and recently biologics (mRNA, siRNA, antigens, antibodies, proteins, and peptides) at targeted sites. The physical and chemical properties of SNP such as large specific surface area, tuneable particle size and porosity, excellent biodegradability and biocompatibility make them an ideal drug delivery and diagnostic platform. Based on the available data and the pre-clinical performance of SNP, recent interest has driven these innovative materials towards clinical application with many of the formulations already in Phase I and Phase II trials. Herein, the progress of SNP in biomedical field is reviewed, and their safety aspects are analysed. Importantly, we critically evaluate the key structural characteristics of SNP to overcome different biological barriers including the blood-brain barrier (BBB), skin, tumour barrier and mucosal barrier. Future directions, potential pathways, and target areas towards rapid clinical translation of SNP are also recommended.

Towards a simple in vitro surface chemistry pre-screening method for nanoparticles to be used for drug delivery to solid tumours.

An efficient nanoparticulate drug carrier intended for chemotherapy based on intravenous administration must exhibit a long enough blood circulation time, a good penetrability into the tumour volume, as well as an efficient uptake by cancer cells. Limiting factors for the therapeutic outcome in vivo are recognition of the nanoparticles as foreign objects, which triggers nanoparticle uptake by defence organs rich in macrophages, e.g. liver and spleen, on the time-scale of accumulation and uptake in/by the tumour. However, the development of nanomedicine towards efficient nanoparticle-based delivery to solid tumours is hampered by the lack of simple, reproducible, cheap, and predictive means for early identification of promising nanoparticle formulations. The surface chemistry of nanoparticles is known to be the most important determinant for the biological fate of nanoparticles, as it influences the extent of serum protein adsorption, and also the relative composition of the protein corona. Here we preliminarily evaluate an extremely simple screening method for nanoparticle surface chemistry pre-optimization based on nanoparticle uptake in vitro by PC-3 cancer cells and THP-1 macrophages. Only when both selectivity for the cancer cells as well as the extent of nanoparticle uptake are taken into consideration do the in vitro results mirror literature results obtained for small animal models. Furthermore, although not investigated here, the screening method does also lend itself to the study of actively targeted nanoparticles.

Virus-like silica nanoparticles enhance macromolecule permeation in vivo.

Nanoparticle based permeation enhancers have the potential to improve the oral delivery of biologics. Recently, solid silica nanoparticles were discovered to improve the intestinal permeability of peptides and proteins via transient opening of the gut epithelium. In this study, we have developed small-sized (∼60 nm) virus-like silica nanoparticles (VSNP) as a reversible and next generation non-toxic permeation enhancer for oral delivery of biologics. Our results show that the anionic VSNP showed a better permeation-enhancing effect than the same sized spherical Stöber silica nanoparticles (∼60 nm) by enhancing the apparent insulin permeability by 1.3-fold in the Caco-2 monolayer model and by 1.2-fold in the Caco-2/MTX-HT-29 co-culture model. In vivo experiments in healthy mice demonstrated that anionic VSNP significantly enhanced the permeation of fluorescently labelled 4 kDa dextran after oral administration compared to Stöber nanoparticles and positively charged VSNP. The results indicated that the nanoscale surface roughness is an important consideration when designing nanoparticle-based permeation enhancers. Overall, our study shows for the first time that small-sized (∼60 nm) VSNP with nanoscale surface roughness can be used as a non-toxic permeation enhancer for oral delivery of therapeutic peptides and proteins.

Straightforward adsorption-based formulation of mesoporous silica nanoparticles for drug delivery applications.

Mesoporous silica nanoparticles (MSNs) have emerged as a very promising drug delivery platform. However, multi-step synthesis and surface functionalization protocols rise the hurdle for translation of this promising drug delivery platform to the clinic. Furthermore, surface functionalization aiming at enhancing the blood circulation time, typically through surface functionalization with poly(ethylene glycol) (PEG) (PEGylation), has repeatedly been shown to be detrimental for the drug loading levels that can be achieved. Here, we present results related to sequential adsorptive drug loading and adsorptive PEGylation, where the conditions can be chosen so that the drug desorption during PEGylation is minimized. At the heart of the approach is the high solubility of PEG both in water and in apolar solvents, which makes it possible to use a solvent for PEGylation in which the drug exhibits a low solubility, as demonstrated here for two model drugs, one being water soluble and the other not. Analysis of the influence of PEGylation on the extent of serum protein adsorption underline the promise of the approach, and the results also allow the adsorption mechanisms to be elaborated. Detailed analysis of the adsorption isotherms enables determination of the fractions of PEG residing on the outer particle surfaces in comparison to inside the mesopore systems, and also makes it possible to determine the PEG conformation on the outer particle surfaces. Both parameters are directly reflected in the extent of protein adsorption to the particles. Finally, the PEG coating is shown to be stable on time-scales compatible with intravenous drug administration, which is why we are convinced that the presented approach or modifications thereof will pave the way for faster translation of this drug delivery platform to the clinic.

Investigation of the Mechanism of SiO2 Particle and Capsule Formation at the Oil-Water Interface of Dye-Stabilized Emulsions.

In a previous contribution we described the formation of silica nanostructures in dye-stabilized nanoemulsions from tetraethyl orthosilicate droplets in water. Depending on the type of dye, either capsules (crystal violet, CV) or nanoparticles (congo red, CR) are formed. The thorough study of the sol-gel process uses a combination of time- and/or temperature-resolved small-angle X-ray scattering, transmission electron microscopy, and 1H NMR spectroscopy to elucidate the detailed kinetics and mechanism of structure formation. In both cases, small nuclei of 1.5-2 nm are formed, followed by either a fast cluster-cluster (CV) or a much slower monomer-cluster aggregation (CR). The former leads to a cross-linked network and finally to patchy capsules, while the latter leads to individual nanoparticles (SNPs). From an Avrami plot it can be deduced that the SNPs are formed by an interface-controlled one-dimensional growth process. The mechanisms are based on the different local environments at the oil-water interface, which is either slightly acidic (CV) or fairly basic (CR). The kinetics differ by a factor between 3 and 20 and are presumably caused by the different mobility of the catalyzing species H+ or OH-.

Enhanced Electrochemical Capacity of Spherical Co-Free Li1.2 Mn0.6 Ni0.2 O2 Particles after a Water and Acid Treatment and its Influence on the Initial Gas Evolution Behavior.

Li-rich layered oxides (LRLO) with specific energies beyond 900 Wh kg-1 are one promising class of high-energy cathode materials. Their high Mn-content allows reducing both costs and the environmental footprint. In this work, Co-free Li1.2 Mn0.6 Ni0.2 O2 was investigated. A simple water and acid treatment step followed by a thermal treatment was applied to the LRLO to reduce surface impurities and to establish an artificial cathode electrolyte interface. Samples treated at 300 °C show an improved cycling behavior with specific first cycle capacities of up to 272 mAh g-1 , whereas powders treated at 900 °C were electrochemically deactivated due to major structural changes of the active compounds. Surface sensitive analytical methods were used to characterize the structural and chemical changes compared to the bulk material. Online DEMS measurements were conducted to get a deeper understanding of the effect of the treatment strategy on O2 and CO2 evolution during electrochemical cycling.

Dissolution and morphology evolution of mesoporous silica nanoparticles under biologically relevant conditions.

Mesoporous silica nanoparticles (MSN) are promising drug vectors due to their high drug loading capacities, degradability under biologically relevant conditions. The dissolution of MSN has been the focus of several recent studies, most of which have, however, been carried out in the absence of proteins, and do therefore not reflect the conditions prevailing during in vitro or in vivo administration of the particles. Furthermore, typically the dissolution studies are limited with respect to the range of MSN concentrations applied. Here, we report results related to the dissolution kinetics and structural particle evolution for MCM-48 MSN carried out in the presence of proteins, and where the particle concentration has been used as a parameter to cover typical concentrations used in in vitro and in vivo studies involving MSNs. Proteins adsorbing to the MSN surface form a diffusion limiting layer that leads to the intermediate formation of core-shell structured particles upon dissolution. Here, the protein concentration controls the kinetics of this process, as the amount of protein adsorbing to the MSN increase with increasing protein concentration. The results thus also imply that the MSN dissolution kinetics is faster under normally applied in vitro conditions as compared to what can be expected under full serum conditions.

Delivery by Dendritic Mesoporous Silica Nanoparticles Enhances the Antimicrobial Activity of a Napsin-Derived Peptide Against Intracellular Mycobacterium tuberculosis.

Tuberculosis remains a serious global health problem causing 1.3 million deaths annually. The causative pathogen Mycobacterium tuberculosis (Mtb) has developed several mechanisms to evade the immune system and resistances to many conventional antibiotics, so that alternative treatment strategies are urgently needed. By isolation from bronchoalveolar lavage and peptide optimization, a new antimicrobial peptide named NapFab is discovered. While showing robust activity against extracellular Mtb, the activity of NapFab against intracellular bacteria is limited due to low intracellular availability. By loading NapFab onto dendritic mesoporous silica nanoparticles (DMSN) as a carrier system, cellular uptake, and consequently antimycobacterial activity against intracellular Mtb is significantly enhanced. Furthermore, using lattice light-sheet fluorescence microscopy, it can be shown that the peptide is gradually released from the DMSN inside living macrophages over time. By electron microscopy and tomography, it is demonstrated that peptide loaded DMSN are stored in vesicular structures in proximity to mycobacterial phagosomes inside the cells, but the nanoparticles are typically not in direct contact with the bacteria. Based on the combination of functional and live-cell imaging analyses, it is hypothesized that after being released from the DMSN NapFab is able to enter the bacterial phagosome and gain access to the bacilli.

Photoactive Titanium Dioxide Films with Embedded Gold Nanoparticles for Quantitative Determination of Mercury Traces in Humic Matter-Containing Freshwaters.

Mercury detection in humic matter-containing natural waters is often associated with environmental harmful substances for sample preparation. Herein we report an approach based on photoactive titanium dioxide films with embedded gold nanoparticles (AuNP@TiO2 dipstick) for chemical-free sample preparation and mercury preconcentration. For this purpose, AuNPs are immobilized onto a silicon wafer and further covered with a thin photoactive titanium dioxide layer. The AuNPs allow the preconcentration of Hg traces via amalgamation, while TiO2 acts as a protective layer and, at the same time, as a photocatalyst for UV-C radiation-based sample pretreatment. Humic matter, often present in natural waters, forms stabile complexes with Hg and so hinders its preconcentration prior to detection, causing a minor recovery. This problem is solved here by irradiation during Hg preconcentration onto the photoactive dipstick, resulting in a limit of detection as low as 0.137 ng L-1 using atomic fluorescence spectrometry (AFS). A 5 min preconcentration step is sufficient to obtain successful recovery of Hg traces from waters with up to 10 mg L-1 DOC. The feasibility of the approach was demonstrated by the determination of Hg traces in Danube river water. The results show no significant differences in comparison with standard cold vapor-atomic fluorescence spectrometry (CV-AFS) measurements of the same sample. Hence, this new AuNP@TiO2 dipstick provides a single-step sample preparation and preconcentration approach that combines sustainability with high analytical sensitivity and accuracy.

On the importance of the linking chemistry for the PEGylation of mesoporous silica nanoparticles.

The typical method for minimizing serum protein adsorption in biological settings and prolonging blood circulation time of nanoparticles, is to anchor hydrophilic polymers (e.g., poly(ethylene glycol), PEG) on the particle surface, which is most often done by covalent attachment (PEGylation). Herein, different PEGylation methods were realised and compared to functionalize mesoporous silica nanoparticles (MSNs). First, reactive groups were installed using post-grafting procedures with different functional silanes. Further, PEGs carrying a functional group and having different chain lengths and termini, were used. The grafting efficacy as well as the structural and physicochemical characteristics of the resulting particles were determined. Finally, the serum protein adsorption behaviour of these functionalized particles was investigated using thermogravimetric analysis. The type of selected coupling method was shown to strongly influence the grafting efficiency as well as the resulting protein adsorption. The results highlight the importance of the right choice of the linking chemistry when aiming at surface functionalization of nanoparticles.

In vitro Targetability Validation of Peptide-Functionalized Mesoporous Silica Nanoparticles in the Presence of Serum Proteins.

Demonstration of receptor-mediated targeting of nanoparticles to specific organs and/or cell types is an integral aim in many bionanomedicine development projects. However, engagement of targeted receptors with ligands on nanocarriers, which is the cornerstone of the active targeting concept, is challenging to study under biologically relevant conditions and thus often stays overlooked. In this work, we utilize an in-house established bioassay for in vitro targetability validation of mesoporous silica nanoparticles (MSNs), functionalized with high-affinity peptide ligands to somatostatin receptors via protective group chemistry, ensuring the correct orientation of the peptide's pharmacophore. We demonstrate that targeted nanoparticles, but not scrambled peptide-decorated counterparts, specifically engage the targeted receptors in living cells in culture media containing serum protein. The importance of being able to exclude false positives originating from the premature detachment of targeting peptides from the MSNs is highlighted.

Silica nanoparticles: A promising platform for enhanced oral delivery of macromolecules.

Oral ingestion remains as the most convenient route of administration for the application of pharmaceuticals since it is non-invasive and does not require trained personnel to administer the drugs. Despite significant progress in novel oral drug delivery platforms over the past few decades, the oral delivery of macromolecules (particularly for peptides and proteins) is one of the major challenges faced by the biopharmaceutical industry. This is even more important since a large number of biologic drugs have been available in the past decade which typically require intravenous administration. Recently, silica nanoparticles have emerged as multifunctional, biocompatible and biodegradable inorganic nanocarriers with enormous potential as an oral drug delivery platform for various therapeutics including macromolecules. Their unique structural composition facilitates the loading of large therapeutic payloads at desired loading capacities for a controlled and site-specific oral delivery. Here, we review first the physiological challenges for oral delivery of peptides and proteins. Next, we discuss silica-based functional materials for oral delivery of macromolecules and highlight their evolving role not only as an encapsulant but as a permeation enhancer as well. Lastly, we also discuss potential strategies for future translation of these novel materials to the clinic.

Multi-Modal PET and MR Imaging in the Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) Model for Initial in Vivo Testing of Target-Specific Radioligands.

The validation of novel target-specific radioligands requires animal experiments mostly using mice with xenografts. A pre-selection based on a simpler in vivo model would allow to reduce the number of animal experiments, in accordance with the 3Rs principles (reduction, replacement, refinement). In this respect, the chick embryo or hen's egg test-chorioallantoic membrane (HET-CAM) model is of special interest, as it is not considered an animal until day 17. Thus, we evaluated the feasibility of quantitative analysis of target-specific radiotracer accumulation in xenografts using the HET-CAM model and combined positron emission tomography (PET) and magnetic resonance imaging (MRI). For proof-of-principle we used established prostate-specific membrane antigen (PSMA)-positive and PSMA-negative prostate cancer xenografts and the clinically widely used PSMA-specific PET-tracer [68Ga]Ga-PSMA-11. Tracer accumulation was quantified by PET and tumor volumes measured with MRI (n = 42). Moreover, gamma-counter analysis of radiotracer accumulation was done ex-vivo. A three- to five-fold higher ligand accumulation in the PSMA-positive tumors compared to the PSMA-negative tumors was demonstrated. This proof-of-principle study shows the general feasibility of the HET-CAM xenograft model for target-specific imaging with PET and MRI. The ultimate value for characterization of novel target-specific radioligands now has to be validated in comparison to mouse xenograft experiments.

Biphenyl-Bridged Organosilica as a Precursor for Mesoporous Silicon Oxycarbide and Its Application in Lithium and Sodium Ion Batteries.

Silicon oxycarbides (SiOC) are an interesting alternative to state-of-the-art lithium battery anode materials, such as graphite, due to potentially higher capacities and rate capabilities. Recently, it was also shown that this class of materials shows great prospects towards sodium ion batteries. Yet, bulk SiOCs are still severely restricted with regard to their electrochemical performance. In the course of this work, a novel and facile strategy towards the synthesis of mesoporous and carbon-rich SiOC will be presented. To achieve this goal, 4,4'-bis(triethoxysilyl)-1,1'-biphenyl was sol-gel processed in the presence of the triblock copolymer Pluronic P123. After the removal of the surfactant using Soxhlet extraction the organosilica material was subsequently carbonized under an inert gas atmosphere at 1000 °C. The resulting black powder was able to maintain all structural features and the porosity of the initial organosilica precursor making it an interesting candidate as an anode material for both sodium and lithium ion batteries. To get a detailed insight into the electrochemical properties of the novel material in the respective battery systems, electrodes from the nanostructured SiOC were studied in half-cells with galvanostatic charge/discharge measurements. It will be shown that nanostructuring of SiOC is a viable strategy in order to outperform commercially applied competitors.

Effective delivery of the anti-mycobacterial peptide NZX in mesoporous silica nanoparticles.

BACKGROUND: Intracellular delivery of antimicrobial agents by nanoparticles, such as mesoporous silica particles (MSPs), offers an interesting strategy to treat intracellular infections. In tuberculosis (TB), Mycobacterium tuberculosis avoids components of the immune system by residing primarily inside alveolar macrophages, which are the desired target for TB therapy. METHODS AND FINDINGS: We have previously identified a peptide, called NZX, capable of inhibiting both clinical and multi-drug resistant strains of M. tuberculosis at therapeutic concentrations. In this study we analysed the potential of MSPs containing NZX for the treatment of tuberculosis. The MSPs released functional NZX gradually into simulated lung fluid and the peptide filled MSPs were easily taken up by primary macrophages. In an intracellular infection model, the peptide containing particles showed increased mycobacterial killing compared to free peptide. The therapeutic potential of peptide containing MSPs was investigated in a murine infection model, showing that MSPs preserved the effect to eliminate M. tuberculosis in vivo. CONCLUSIONS: In this study we found that loading the antimicrobial peptide NZX into MSPs increased the inhibition of intracellular mycobacteria in primary macrophages and preserved the ability to eliminate M. tuberculosis in vivo in a murine model. Our studies provide evidence for the feasibility of using MSPs for treatment of tuberculosis.

Cell adherence and drug delivery from particle based mesoporous silica films.

Spatially and temporally controlled drug delivery is important for implant and tissue engineering applications, as the efficacy and bioavailability of the drug can be enhanced, and can also allow for drugging stem cells at different stages of development. Long-term drug delivery over weeks to months is however difficult to achieve, and coating of 3D surfaces or creating patterned surfaces is a challenge using coating techniques like spin- and dip-coating. In this study, mesoporous films consisting of SBA-15 particles grown onto silicon wafers using wet processing were evaluated as a scaffold for drug delivery. Films with various particle sizes (100-900 nm) and hence thicknesses were grown onto trichloro(octadecyl)silane-functionalized silicon wafers using a direct growth method. Precise patterning of the areas for film growth could be obtained by local removal of the OTS functionalization through laser ablation. The films were incubated with the drug model 3,3'-dioctadecyloxacarbocyanine perchlorate (DiO), and murine myoblast cells (C2C12 cells) were seeded onto films with different particle sizes. Confocal laser scanning microscopy (CLSM) was used to study the cell growth, and a vinculin-mediated adherence of C2C12 cells on all films was verified. The successful loading of DiO into the films was confirmed by UV-vis and CLSM. It was observed that the drugs did not desorb from the particles during 24 hours in cell culture. During adherent growth on the films for 4 h, small amounts of DiO and separate particles were observed inside single cells. After 24 h, a larger number of particles and a strong DiO signal were recorded in the cells, indicating a particle mediated drug uptake. The vast majority of the DiO-loaded particles remained attached to the substrate also after 24 h of incubation, making the films attractive as longer-term reservoirs for drugs on e.g. medical implants.

Influence of serum concentration and surface functionalization on the protein adsorption to mesoporous silica nanoparticles.

A study of a protein corona on mesoporous silica nanoparticles (MSNs) at in vitro and in vivo relevant serum concentrations is presented. Three MSNs different in terms of mesoscopic pore arrangement, surface chemistry, and surface roughness were studied. After incubation in either 10% or 100% serum, the hard protein corona-particle complexes were collected and analyzed by DLS, zeta-potential, and TGA, and the corona proteins were analyzed with SDS-PAGE. A good correlation between SDS-PAGE and TG results in terms of total amounts of proteins adsorbed was established. The results demonstrated that more proteins, especially apolipoproteins, were associated with the particles at higher serum concentration regardless of surface chemistry and morphological differences. Also, the mean molecular weight of the adsorbed proteins was clearly lower under full serum conditions modeling in vivo conditions as compared to under dilute conditions modeling in vitro conditions, but functionalization of the MSNs by carboxylic acid functionalities reduced protein adsorption. The influence of the structural characteristics of the MSNs on the protein adsorption was minor.

Quantitative 19F MRI of perfluoro-15-crown-5-ether using uniformity correction of the spin excitation and signal reception.

OBJECTIVES: A common limitation of all 1H contrast agents is that they only allow indirect visualization through modification of the intrinsic properties of the tissue, making quantification of this effect challenging. 19F compounds, on the contrary, are measured directly, without any background signal. There is a linear relationship between the amount of 19F spins and the intensity of the signal. However, non-uniformity of the radiofrequency field may lead to errors in the quantified 19F signal and should be carefully addressed for any quantitative imaging. MATERIALS AND METHODS: Adaptation of the previously introduced [Formula: see text] mapping technique to the problem of quantifying the 19F signal from perfluoro-15-crown-5-ether (PFCE) is proposed in this work. Initial evaluation of the proposed technique simultaneously accounting for transmit [Formula: see text] and receive [Formula: see text] field inhomogeneities is performed in a PFCE phantom. As a proof of concept, in vivo quantification of the 19F signal is performed in a murine model after application of custom-designed hollow mesoporous silica spheres (HMSS) loaded with PFCE. RESULTS: A phantom experiment clearly shows that only compensation for both transmit and receive characteristics outperforms inaccurate quantification based on the non- or partly-corrected signal intensities. Furthermore, an optimized protocol is proposed for in vivo application. CONCLUSION: The proposed [Formula: see text]/[Formula: see text] mapping technique represents a simple to implement and easy-to-use solution for quantification of the 19F signal from PFCE in the presence of B1-field inhomogeneities.