Switching the Chemoselectivity in the Preparation of [18F]FNA-N-CooP, a Free Thiol-Containing Peptide for Targeted Positron Emission Tomography Imaging of Fatty Acid Binding Protein 3.

Fatty acid binding protein 3 (FABP3) is expressed both in tumor cells and in the tumor vasculature, making it a potential target for medical imaging and therapy. In this study, we aimed to radiolabel a CooP peptide with a free amino and thiol group, and evaluate the radiolabeled product [18F]FNA-N-CooP for imaging FABP3 expression in breast cancer brain metastases by positron emission tomography. [18F]FNA-N-CooP was prepared by highly chemoselective N-acylation and characterized using different chemical approaches. We validated its binding to the target using in vitro tissue section autoradiography and performed stability tests in vitro and in vivo. [18F]FNA-N-CooP was successfully synthesized in 16.8% decay-corrected radiochemical yield with high radiochemical purity (98.5%). It exhibited heterogeneous binding on brain metastasis tissue sections from a patient with breast cancer, with foci of radioactivity binding corresponding to FABP3 positivity. Furthermore, the tracer binding was reduced by 55% in the presence of nonradioactive FNA-N-CooP a blocker, indicating specific tracer binding and that FABP3 is a viable target for [18F]FNA-N-CooP. Favorably, the tracer did not bind to necrotic tumor tissue. However, [18F]FNA-N-CooP displayed limited stability both in vitro in mouse plasma or human serum and in vivo in mouse, therefore further studies are needed to improve the stability [18F]FNA-N-CooP to be used for in vivo applications.

Aqueous Processable One-Dimensional Polypyrrole Nanostructured by Lignocellulose Nanofibril: A Conductive Interfacing Biomaterial.

One-dimensional (1D) nanomaterials of conductive polypyrrole (PPy) are competitive biomaterials for constructing bioelectronics to interface with biological systems. Synergistic synthesis using lignocellulose nanofibrils (LCNF) as a structural template in chemical oxidation of pyrrole with Fe(III) ions facilitates surface-confined polymerization of pyrrole on the nanofibril surface within a submicrometer- and micrometer-scale fibril length. It yields a core-shell nanocomposite of PPy@LCNF, wherein the surface of each individual fibril is coated with a thin nanoscale layer of PPy. A highly positive surface charge originating from protonated PPy gives this 1D nanomaterial a durable aqueous dispersity. The fibril-fibril entanglement in the PPy@LCNFs facilely supported versatile downstream processing, e.g., spray thin-coating on glass, flexible membranes with robust mechanics, or three-dimensional cryogels. A high electrical conductivity in the magnitude of several to 12 S·cm-1 was confirmed for the solid-form PPy@LCNFs. The PPy@LCNFs are electroactive and show potential cycling capacity, encompassing a large capacitance. Dynamic control of the doping/undoping process by applying an electric field combines electronic and ionic conductivity through the PPy@LCNFs. The low cytotoxicity of the material is confirmed in noncontact cell culture of human dermal fibroblasts. This study underpins the promises for this nanocomposite PPy@LCNF as a smart platform nanomaterial in constructing interfacing bioelectronics.

Functionalized and Nonfunctionalized Nanosystems for Mitochondrial Drug Delivery with Metallic Nanoparticles.

Background: The application of metallic nanoparticles as a novel therapeutic tool has significant potential to facilitate the treatment and diagnosis of mitochondria-based disorders. Recently, subcellular mitochondria have been trialed to cure pathologies that depend on their dysfunction. Nanoparticles made from metals and their oxides (including gold, iron, silver, platinum, zinc oxide, and titanium dioxide) have unique modi operandi that can competently rectify mitochondrial disorders. Materials: This review presents insight into the recent research reports on exposure to a myriad of metallic nanoparticles that can alter the dynamic ultrastructure of mitochondria (via altering metabolic homeostasis), as well as pause ATP production, and trigger oxidative stress. The facts and figures have been compiled from more than a hundred PubMed, Web of Science, and Scopus indexed articles that describe the essential functions of mitochondria for the management of human diseases. Result: Nanoengineered metals and their oxide nanoparticles are targeted at the mitochondrial architecture that partakes in the management of a myriad of health issues, including different cancers. These nanosystems not only act as antioxidants but are also fabricated for the delivery of chemotherapeutic agents. However, the biocompatibility, safety, and efficacy of using metal nanoparticles is contested among researchers, which will be discussed further in this review.

The Antioxidative Effects of Picein and Its Neuroprotective Potential: A Review of the Literature.

Neurodegenerative diseases (NDDs) are the main cause of dementia in the elderly, having no cure to date, as the currently available therapies focus on symptom remission. Most NDDs will progress despite treatment and eventually result in the death of the patient after several years of a burden on both the patient and the caregivers. Therefore, it is necessary to investigate agents that tackle the disease pathogenesis and can efficiently slow down or halt disease progression, with the hope of curing the patients and preventing further burden and mortality. Accordingly, recent research has focused on disease-modifying treatments with neuroregenerative or neuroprotective effects. For this purpose, it is necessary to understand the pathogenesis of NDDs. It has been shown that oxidative stress plays an important role in the damage to the central nervous system and the progression of neurodegenerative disorders. Furthermore, mitochondrial dysfunction and the accumulation of unfolded proteins, including beta-amyloid (Aß), tau proteins, and α-synuclein, have been suggested. Accordingly, cellular and molecular studies have investigated the efficacy of several natural compounds (herbs and nutritional agents) for their neuroprotective and antioxidative properties. The most popular herbs suggested for the treatment and/or prevention of NDDs include Withania somnifera (ashwagandha), ginseng, curcumin, resveratrol, Baccopa monnieri, and Ginkgo biloba. In some herbs, such as ginseng, preclinical and clinical evidence are available for supporting its effectiveness; however, in some others, only cellular and animal studies are available. In line with the scant literature in terms of the effectiveness of herbal compounds on NDDs, there are also other herbal agents that have been disregarded. Picein is one of the herbal agents that has been investigated in only a few studies. Picein is the active ingredient of several herbs and can be thus extracted from different types of herbs, which makes it more available. It has shown to have anti-inflammatory properties in cellular and plant studies; however, to date, only one study has suggested its neuroprotective properties. Furthermore, some cellular studies have shown no anti-inflammatory effect of picein. Therefore, a review of the available literature is required to summarize the results of studies on picein. To date, no review study seems to have addressed this issue. Thus, in the present study, we gather the available information about the antioxidative and potential neuroprotective properties of picein and its possible effectiveness in treating NDDs. We also summarize the plants from which picein can be extracted in order to guide researchers for future investigations.

Small-Molecule-based Supramolecular Plastics Mediated by Liquid-Liquid Phase Separation.

Plastics are one of the most widely used polymeric materials. However, they are often undegradable and non-recyclable due to the very stable covalent bonds of macromolecules, causing environmental pollution and health problems. Here, we report that liquid-liquid phase separation (LLPS) could drive the formation of robust, stable, and sustainable plastics using small molecules. The LLPS process could sequester and concentrate solutes, strengthen the non-covalent association between molecules and produce a bulk material whose property was highly related to the encapsulated water amounts. It was a robust plastic with a remarkable Young's modulus of 139.5 MPa when the water content was low while became adhesive and could instantly self-heal with more absorbed water. Finally, responsiveness enabled the material to be highly recyclable. This work allowed us to understand the LLPS at the molecular level and demonstrated that LLPS is a promising approach to exploring eco-friendly supramolecular plastics that are potential substitutes for conventional polymers.

Peritumoral Microgel Reservoir for Long-Term Light-Controlled Triple-Synergistic Treatment of Osteosarcoma with Single Ultra-Low Dose.

Local minimally invasive injection of anticancer therapies is a compelling approach to maximize the utilization of drugs and reduce the systemic adverse drug effects. However, the clinical translation is still hampered by many challenges such as short residence time of therapeutic agents and the difficulty in achieving multi-modulation combination therapy. Herein, mesoporous silica-coated gold nanorods (AuNR@SiO2 ) core-shell nanoparticles are fabricated to facilitate drug loading while rendering them photothermally responsive. Subsequently, AuNR@SiO2 is anchored into a monodisperse photocrosslinkable gelatin (GelMA) microgel through one-step microfluidic technology. Chemotherapeutic drug doxorubicin (DOX) is loaded into AuNR@SiO2 and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) is loaded in the microgel layer. The osteosarcoma targeting ligand alendronate is conjugated to AuNR@SiO2 to improve the tumor targeting. The microgel greatly improves the injectability since they can be dispersed in buffer and the injectability and degradability are adjustable by microfluidics during the fabrication. The drug release can, in turn, be modulated by multi-round light-trigger. Importantly, a single super low drug dose (1 mg kg-1 DOX with 5 mg kg-1 DMXAA) with peritumoral injection generates long-term therapeutic effect and significantly inhibited tumor growth in osteosarcoma bearing mice. Therefore, this nanocomposite@microgel system can act as a peritumoral reservoir for long-term effective osteosarcoma treatment.

Mesoporous Silica Nanoparticles as Carriers for Biomolecules in Cancer Therapy.

Mesoporous silica nanoparticles (MSNs) offer many advantageous properties for applications in the field of nanobiotechnology. Loading of small molecules into MSNs is straightforward and widely applied, but with the upswing of both research and commercial interest in biological drugs in recent years, also biomacromolecules have been loaded into MSNs for delivery purposes. MSNs possess many critical properties making them a promising and versatile carrier for biomacromolecular delivery. In this chapter, we review the effects of the various structural parameters of MSNs on the effective loading of biomacromolecular therapeutics, with focus on maintaining stability and drug delivery performance. We also emphasize recent studies involving the use of MSNs in the delivery of biomacromolecular drugs, especially for cancer treatment.

3D Modeling of Epithelial Tumors-The Synergy between Materials Engineering, 3D Bioprinting, High-Content Imaging, and Nanotechnology.

The current statistics on cancer show that 90% of all human cancers originate from epithelial cells. Breast and prostate cancer are examples of common tumors of epithelial origin that would benefit from improved drug treatment strategies. About 90% of preclinically approved drugs fail in clinical trials, partially due to the use of too simplified in vitro models and a lack of mimicking the tumor microenvironment in drug efficacy testing. This review focuses on the origin and mechanism of epithelial cancers, followed by experimental models designed to recapitulate the epithelial cancer structure and microenvironment, such as 2D and 3D cell culture models and animal models. A specific focus is put on novel technologies for cell culture of spheroids, organoids, and 3D-printed tissue-like models utilizing biomaterials of natural or synthetic origins. Further emphasis is laid on high-content imaging technologies that are used in the field to visualize in vitro models and their morphology. The associated technological advancements and challenges are also discussed. Finally, the review gives an insight into the potential of exploiting nanotechnological approaches in epithelial cancer research both as tools in tumor modeling and how they can be utilized for the development of nanotherapeutics.

Self-Synthesizing Nanorods from Dynamic Combinatorial Libraries against Drug Resistant Cancer.

Molecular self-assembly has been widely used to develop nanocarriers for drug delivery. However, most of them have unsatisfactory drug loading capacity (DLC) and the dilemma between stimuli-responsiveness and stability, stagnating their translational process. Herein, we overcame these drawbacks using dynamic combinatorial chemistry. A carrier molecule was spontaneously and quantitatively synthesized, aided by co-self-assembly with a template molecule and an anti-cancer drug doxorubicin (DOX) from a dynamic combinatorial library that was operated by disulfide exchange under thermodynamic control. The highly selective synthesis guaranteed a stable yet pH- and redox- responsive nanocarrier with a maximized DLC of 40.1 % and an enhanced drug potency to fight DOX resistance in vitro and in vivo. Our findings suggested that harnessing the interplay between synthesis and self-assembly in complex chemical systems could yield functional nanomaterials for advanced applications.

Fluorescent and Electron-Dense Green Color Emitting Nanodiamonds for Single-Cell Correlative Microscopy.

Correlative light and electron microscopy (CLEM) is revolutionizing how cell samples are studied. CLEM provides a combination of the molecular and ultrastructural information about a cell. For the execution of CLEM experiments, multimodal fiducial landmarks are applied to precisely overlay light and electron microscopy images. Currently applied fiducials such as quantum dots and organic dye-labeled nanoparticles can be irreversibly quenched by electron beam exposure during electron microscopy. Generally, the sample is therefore investigated with a light microscope first and later with an electron microscope. A versatile fiducial landmark should offer to switch back from electron microscopy to light microscopy while preserving its fluorescent properties. Here, we evaluated green fluorescent and electron dense nanodiamonds for the execution of CLEM experiments and precisely correlated light microscopy and electron microscopy images. We demonstrated that green color emitting fluorescent nanodiamonds withstand electron beam exposure, harsh chemical treatments, heavy metal straining, and, importantly, their fluorescent properties remained intact for light microscopy.

Comparison of Polydopamine-Coated Mesoporous Silica Nanorods and Spheres for the Delivery of Hydrophilic and Hydrophobic Anticancer Drugs.

Mesoporous silica nanoparticles (MSNs) have been widely studied as drug delivery systems in nanomedicine. Surface coating of MSNs have enabled them to perform efficiently in terms of bioavailability, biocompatibility, therapeutic efficacy and targeting capability. Recent studies have suggested the use of polydopamine (PDA) as a facilitative coating for MSNs that provides sustained and pH-responsive drug release, owing to the adhesive "molecular-glue" function of PDA. This further endows these hybrid MSN@PDA particles with the ability to carry large amounts of hydrophilic drugs. In this study, we expand the feasibility of this platform in terms of exploring its ability to also deliver hydrophobic drugs, as well as investigate the effect of particle shape on intracellular delivery of both a hydrophilic and hydrophobic anticancer drug. MSN@PDA loaded with doxorubicin (hydrophilic) and fingolimod (hydrophobic) was studied via a systematic in vitro approach (cellular internalization, intracellular drug distribution and cytotoxicity). To promote the cellular uptake of the MSN@PDA particles, they were further coated with a polyethylene imine (PEI)-polyethylene glycol (PEG) copolymer. Drug-loaded, copolymer-coated MSN@PDA showed effective cellular uptake, intracellular release and an amplified cytotoxic effect with both doxorubicin and fingolimod. Additionally, rods exhibited delayed intracellular drug release and superior intracellular uptake compared to spheres. Hence, the study provides an example of how the choice and design of drug delivery systems can be tuned by the need for performance, and confirms the PDA coating of MSNs as a useful drug delivery platform beyond hydrophilic drugs.

STED-TEM Correlative Microscopy Leveraging Nanodiamonds as Intracellular Dual-Contrast Markers.

Development of fluorescent and electron dense markers is essential for the implementation of correlative light and electron microscopy, as dual-contrast landmarks are required to match the details in the multimodal images. Here, a novel method for correlative microscopy that utilizes fluorescent nanodiamonds (FNDs) as dual-contrast probes is reported. It is demonstrated how the FNDs can be used as dual-contrast labels-and together with automatic image registration tool SuperTomo, for precise image correlation-in high-resolution stimulated emission depletion (STED)/confocal and transmission electron microscopy (TEM) correlative microscopy experiments. It is shown how FNDs can be employed in experiments with both live and fixed cells as well as simple test samples. The fluorescence imaging can be performed either before TEM imaging or after, as the robust FNDs survive the TEM sample preparation and can be imaged with STED and other fluorescence microscopes directly on the TEM grids.

A method for optical imaging and monitoring of the excretion of fluorescent nanocomposites from the body using artificial neural networks.

In this study, a new approach to the implementation of optical imaging of fluorescent nanoparticles in a biological medium using artificial neural networks is proposed. The studies were carried out using new synthesized nanocomposites - nanometer graphene oxides, covered by the poly(ethylene imine)-poly(ethylene glycol) copolymer and by the folic acid. We present an example of a successful solution of the problem of monitoring the removal of nanocomposites based on nGO and their components with urine using fluorescent spectroscopy and artificial neural networks. However, the proposed method is applicable for optical imaging of any fluorescent nanoparticles used as theranostic agents in biological tissue.

Renewable poly(δ-decalactone) based block copolymer micelles as drug delivery vehicle: in vitro and in vivo evaluation.

Polymers from natural resources are attracting much attention in various fields including drug delivery as green alternatives to fossil fuel based polymers. In this quest, novel block copolymers based on renewable poly(δ-decalactone) (PDL) were evaluated for their drug delivery capabilities and compared with a fossil fuel based polymer i.e. methoxy-poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-b-PCL). Using curcumin as a hydrophobic drug model, micelles of PDL block copolymers with different orientation i.e. AB (mPEG-b-PDL), ABA (PDL-b-PEG-b-PDL), ABC (mPEG-b-PDL-b-poly(pentadecalactone) and (mPEG-b-PCL) were prepared by nanoprecipitation method. The size, drug loading and curcumin stability studies results indicated that mPEG-b-PDL micelles was comparable to its counterpart mPEG-b-PCL micelles towards improved delivery of curcumin. Therefore, mixed micelles using these two copolymers were also evaluated to see any change in size, loading and drug release. Drug release studies proposed that sustained release can be obtained using poly(pentadecalactone) as crystalline core whereas rapid release can be achieved using amorphous PDL core. Further, mPEG-b-PDL micelles were found to be non-haemolytic, up to the concentration of 40 mg/mL. In vivo toxicity studies on rats advised low-toxic behaviour of these micelles up to 400 mg/kg dose, as evident by histopathological and biochemical analysis. In summary, it is anticipated that mPEG-b-PDL block copolymer micelles could serve as a renewable alternative for mPEG-b-PCL copolymers in drug delivery applications.

Ratiometric Sensing and Imaging of Intracellular pH Using Polyethylenimine-Coated Photon Upconversion Nanoprobes.

Measurement of changes of pH at various intracellular compartments has potential to solve questions concerning the processing of endocytosed material, regulation of the acidification process, and also acidification of vesicles destined for exocytosis. To monitor these events, the nanosized optical pH probes need to provide ratiometric signals in the optically transparent biological window, target to all relevant intracellular compartments, and to facilitate imaging at subcellular resolution without interference from the biological matrix. To meet these criteria we sensitize the surface conjugated pH sensitive indicator via an upconversion process utilizing an energy transfer from the nanoparticle to the indicator. Live cells were imaged with a scanning confocal microscope equipped with a low-energy 980 nm laser excitation, which facilitated high resolution and penetration depth into the specimen, and low phototoxicity needed for long-term imaging. Our upconversion nanoparticle resonance energy transfer based sensor with polyethylenimine-coating provides high colloidal stability, enhanced cellular uptake, and distribution across cellular compartments. This distribution was modulated with membrane integrity perturbing treatment that resulted into total loss of lysosomal compartments and a dramatic pH shift of endosomal compartments. These nanoprobes are well suited for detection of pH changes in in vitro models with high biological background fluorescence and in in vivo applications, e.g., for the bioimaging of small animal models.

Lipid Bilayer-Gated Mesoporous Silica Nanocarriers for Tumor-Targeted Delivery of Zoledronic Acid in Vivo.

Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate used for the treatment of bone diseases and calcium metabolism. Anticancer activity of ZOL has been established, but its extraskeletal effects are limited due to its rapid uptake and accumulation to bone hydroxyapatite. In this work, we report on the development of tethered lipid bilayer-gated mesoporous silica nanocarriers (MSNs) for the incorporation, retention, and intracellular delivery of ZOL. The in vitro anticancer activity of ZOL-loaded nanocarriers was evaluated by cell viability assay and live-cell imaging. For in vivo delivery, the nanocarriers were tagged with folic acid to boost the affinity for breast cancer cells. Histological examination of the liver revealed no adverse off-target effects stemming from the nanocarriers. Importantly, nonspecific accumulation of ZOL within bone was not observed, which indicated in vivo stability of the tethered lipid bilayers. Further, the intravenously administered ZOL-loaded nanocarriers showed tumor growth suppression in breast cancer xenograft-bearing mice.

Solution Conformation of Polymer Brushes Determines Their Interactions with DNA and Transfection Efficiency.

Polymer brush-functionalized nanomaterials offer interesting features for the design of gene delivery vectors as their physicochemical and structural properties can be designed independently of the chemistry, size and shape of the nanomaterial core. However, little is known of the parameters regulating the adsorption and infiltration of DNA molecules at the surface of positively charged polymer brushes, despite the importance of such processes for gene delivery. Here we investigate the role of the molecular environment (e.g., pH, type of buffer, concentration) on the interactions between plasmid DNA and positively charged poly(dimethylaminoethyl methacrylate) (PDMAEMA) brushes using a combination of light scattering, electrophoretic light scattering, in situ ellipsometry, and surface plasmon resonance. We show that the conformation of swollen PDMAEMA brushes is modulated by the surrounding buffer and that this impacts strongly on the ability of such brushes and nanomaterials based on these coatings to complex DNA molecules. In turn, the levels of transfection efficiency measured correlate with changes in brush conformation and DNA binding. Therefore, this work demonstrates the importance of molecular design of polymer brushes to control DNA complexation and release in order to optimize the performance of polymer brush-functionalized nanomaterials for gene delivery applications.

Super-sensitive time-resolved fluoroimmunoassay for thyroid-stimulating hormone utilizing europium(III) nanoparticle labels achieved by protein corona stabilization, short binding time, and serum preprocessing.

Thyrotropin or thyroid-stimulating hormone (TSH) is used as a marker for thyroid function. More precise and more sensitive immunoassays are needed to facilitate continuous monitoring of thyroid dysfunctions and to assess the efficacy of the selected therapy and dosage of medication. Moreover, most thyroid diseases are autoimmune diseases making TSH assays very prone to immunoassay interferences due to autoantibodies in the sample matrix. We have developed a super-sensitive TSH immunoassay utilizing nanoparticle labels with a detection limit of 60 nU L-1 in preprocessed serum samples by reducing nonspecific binding. The developed preprocessing step by affinity purification removed interfering compounds and improved the recovery of spiked TSH from serum. The sensitivity enhancement was achieved by stabilization of the protein corona of the nanoparticle bioconjugates and a spot-coated configuration of the active solid-phase that reduced sedimentation of the nanoparticle bioconjugates and their contact time with antibody-coated solid phase, thus making use of the higher association rate of specific binding due to high avidity nanoparticle bioconjugates. Graphical Abstract We were able to decrease the lowest limit of detection and increase sensitivity of TSH immunoassay using Eu(III)-nanoparticles. The improvement was achieved by decreasing binding time of nanoparticle bioconjugates by small capture area and fast circular rotation. Also, we applied a step to stabilize protein corona of the nanoparticles and a serum-preprocessing step with a structurally related antibody.

Inhibiting Notch Activity in Breast Cancer Stem Cells by Glucose Functionalized Nanoparticles Carrying γ-secretase Inhibitors.

Cancer stem cells (CSCs) are a challenge in cancer treatment due to their therapy resistance. We demonstrated that enhanced Notch signaling in breast cancer promotes self-renewal of CSCs that display high glycolytic activity and aggressive hormone-independent tumor growth in vivo. We took advantage of the glycolytic phenotype and the dependence on Notch activity of the CSCs and designed nanoparticles to target the CSCs. Mesoporous silica nanoparticles were functionalized with glucose moieties and loaded with a γ-secretase inhibitor, a potent interceptor of Notch signaling. Cancer cells and CSCs in vitro and in vivo efficiently internalized these particles, and particle uptake correlated with the glycolytic profile of the cells. Nanoparticle treatment of breast cancer transplants on chick embryo chorioallantoic membranes efficiently reduced the cancer stem cell population of the tumor. Our data reveal that specific CSC characteristics can be utilized in nanoparticle design to improve CSC-targeted drug delivery and therapy.

Inkjet Printing of Drug-Loaded Mesoporous Silica Nanoparticles-A Platform for Drug Development.

Mesoporous silica nanoparticles (MSNs) have shown great potential in improving drug delivery of poorly water soluble (BCS class II, IV) and poorly permeable (BCS class III, IV) drugs, as well as facilitating successful delivery of unstable compounds. The nanoparticle technology would allow improved treatment by reducing adverse reactions of currently approved drugs and possibly reintroducing previously discarded compounds from the drug development pipeline. This study aims to highlight important aspects in mesoporous silica nanoparticle (MSN) ink formulation development for digital inkjet printing technology and to advice on choosing a method (2D/3D) for nanoparticle print deposit characterization. The results show that both unfunctionalized and polyethyeleneimine (PEI) surface functionalized MSNs, as well as drug-free and drug-loaded MSN-PEI suspensions, can be successfully inkjet-printed. Furthermore, the model BCS class IV drug remained incorporated in the MSNs and the suspension remained physically stable during the processing time and steps. This proof-of-concept study suggests that inkjet printing technology would be a flexible deposition method of pharmaceutical MSN suspensions to generate patterns according to predefined designs. The concept could be utilized as a versatile drug screening platform in the future due to the possibility of accurately depositing controlled volumes of MSN suspensions on various materials.