Design and synthesis of vancomycin-functionalized ZnFe2 O4 nanoparticles as an effective antibacterial agent against methicillin-resistant Staphylococcus aureus.

The emergence of antibiotic-resistant bacterial infections is a principal threat to global health. Functionalization of nanomaterial with antibiotics is known as a useful method for increasing the effectiveness of existing antibiotics. In this study, vancomycin-functionalized ZnFe2 O4 nanocomposite (ZnFe2 O4 @Cell@APTES@Van) was synthesized, and its functional groups and particle size were characterized using Fourier-transform infrared spectroscopy, thermogravimetric analysis, dynamic light scattering, scanning electron microscope, and transmission electron microscopy. The antibacteria activity of the synthesized nanocomposite was evaluated using minimum inhibitory concentration and minimum bactericidal concentration against Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA). Cytotoxicity assay was done by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide method. Characterization analyses of synthesized nanocomposite confirmed the binding of vancomysin on the surface of ZnFe2 O4 @Cell@APTES. Nanocomposite exhibited an aggregated semi-spherical structure with hydrodynamic radii of ∼382 nm. In vitro antibacterial activity test showed that vancomycin and vancomycin functionalized ZnFe2 O4 have no antibacterial effect against E. coli. S. aureus was sensitive to vancomycin and ZnFe2 O4 @Cell@APTES@Van NPs and ZnFe2 O4 NPs did not improve vancomycin antibacterial activity against these bacteria. MRSA is resistant to vancomycin while ZnFe2 O4 @Cell@APTES@Van NPs was efficient in inhibiting MRSA growth. In summary, this study showed that attachment of vancomycin to ZnFe2 O4 NPs was increased its antibacterial activity against MRSA.

Characteristics of electrospun chitosan/carbon nanotube coatings deposited on AZ31 magnesium alloy.

Mg-based biomaterials are commonly used as biodegradable orthopedic implants (e.g., bone regeneration applications). However, achieving high biocompatibility and corrosion resistance has remained a challenge to be tackled. In this work, to investigate various fabricated coatings (with and without pre- anodizing), five categories of samples are considered: (a) bare Mg alloy (Mg), (b) Anodized Mg alloy (Mg-A), (c) CS-coated Mg alloy (Mg-C), (d) CS-coated anodized Mg alloy (Mg-AC), and (e) CS-CNT-coated anodized Mg alloy (Mg-ACC). These samples were characterized by using Field Emission Scanning Electron Microscopes (FE-SEM), Energy Dispersive Spectroscopy (EDS), Fourier Transform Infrared Spectroscopy (FT-IR), and Raman Spectroscopy. The adhesion within the coated samples was compared. Then, the effects of the coatings were evaluated by comparing wettability, corrosion behavior, and biocompatibility for bare and coated samples. The adhesion test showed that the coatings exhibited higher adhesion for Mg-AC and Mg-ACC compared to Mg-C. Desired wettability was achieved as the contact angles of coated samples were in the range of 55°- 65°. Electrochemical impedance and polarization as well as immersion tests showed higher corrosion resistance for coated samples. The composite coated sample showed improved cell adhesion since the osteoblast cells covered almost the entire surface of the sample. Moreover, osteoblast cell viability for the sample was around 40% higher than that of the bare sample.

The protective effect of N-acetylcysteine against liposome and chitosan-induced cytotoxicity.

AIM: N-acetylcysteine (NAC) is an antioxidant used to moderate liposome and chitosan-induced cell cytotoxicity at their high concentrations. METHODS: Liposome and chitosan were prepared and characterised. The cytotoxicity effect of liposome with NAC-loaded liposome (liposome-NAC) and chitosan solution with chitosan solution containing NAC (chitosan-NAC) on the A549 cell line was compared. RESULTS: Particle size, zeta potential, and NAC drug release for liposome were 125.9 ± 8 nm, -34.7 ± 2.1 mV, and 51.1% ± 3%, respectively. Scanning electron microscope (SEM) and transmission electron microscope (TEM) indicated spherical shape of liposome. Encapsulation efficiency of liposome-NAC was 12% ± 0.98%. Particle size and zeta potential for chitosan solution were 361 ± 11.3 nm and 10.8 ± 1.52 mV. Stability storage study indicated good stability of chitosan and liposome. Cell viability of liposome-NAC and chitosan-NAC significantly was higher than liposome and chitosan at all four concentrations. CONCLUSIONS: NAC has a protective effect against liposome and chitosan-induced cell toxicity.

Synthesis and evaluation of injectable thermosensitive penta-block copolymer hydrogel (PNIPAAm-PCL-PEG-PCL-PNIPAAm) and star-shaped poly(CL─CO─LA)-b-PEG for wound healing applications.

BACKGROUND: Loss of skin integrity due to injury, burning, or illness makes the development of new treatment options necessary. Skin tissue engineering provides some solutions for these problems. OBJECTIVE: The potential of a biodegradable star-shaped copolymer [Poly(CL─CO─LA)-b-PEG] and penta-block copolymer hydrogel (PNIPAAm-PCL-PEG-PCL-PNIPAAm) was assessed for skin tissue engineering applications. METHODS: Two copolymers were synthesized for cellular culture scaffolds and their mechanical properties were compared. The resulting star-shaped copolymer and thermosensitive penta-block copolymer were characterized using Fourier transform infrared and nuclear magnetic resonance spectroscopy. The crystallizability of the two copolymers was analyzed using X-ray diffraction. The resulting thermosensitive penta-block copolymer was evaluated by differential thermal analysis, differential scanning calorimetry and thermogravimetric analysis. Scanning electron microscopy and in vitro degradation of the polymer network in phosphate buffer solutions (pH 7.4) at 37°C were also examined. The pore size of the gels was calculated with Image Analyzer software. Finally, the cytotoxic, morphological, and gene expression effects of copolymers on the skin fibroblast were evaluated. RESULTS: The experiments showed that the PNIPAAm-PCL-PEG-PCL-PNIPAAm polymer with the right composition and the expected molecular weight was achieved. The hydrogel had less crystallizability compared with its precursors. The resulting thermosensitive hydrogel had a three-dimensional structure with interconnected pores that mimicked the extracellular matrix. The control of the degradability rate can be possible by weight percent changes. The pore size correlated with the polymer concentration in aqueous solution and the pore sizes of the 20 wt% hydrogel were better for fibroblast cultivation than those of the 10 wt% hydrogel. Cell proliferation on the 20% gel was more than that of the 10% gel. The hydrogel not only preserved the viability and phenotypical morphology of the entrapped cells but also stimulated the initial cell-cell interactions and proliferation of fibroblasts. The hydrogel did not influence cell conformation and this property of the polymer underlined its safety. Cells seeded on this copolymer showed a normal and spear shape and formed a focal adhesion with the hydrogel surface. Notably, the hydrogel increased collagen I α1 and collagen III mRNAs expression. CONCLUSION: Due to the low molecular weight and poor mechanical strength of the star-shaped copolymer, it was not considered for fabrication of the scaffolds for wound healing. The biodegradable, biocompatible, injectable and thermosensitive PNIPAAm-PCL-PEG-PCL-PNIPAAm hydrogel in 20 wt% demonstrated a desirable potential for future application as a cell scaffold in skin tissue engineering and wound healing.

Porous MnFe2O4@SiO2 magnetic glycopolymer: A multivalent nanostructure for efficient removal of bacteria from aqueous solution.

The focuses of this research is to prepare an efficient magnetic glycopolymer for bacteria removal from aqueous solution. To perform this idea; porous MnFe2O4@SiO2 was functionalized with glucose and or maltose as an anchors to adhere onto bacteria cell surface. Aminopropyltriethoxysilane was employed to link the saccharides on magnetic nanoparticle surface. The hybrid materials were characterized with XRD, VSM, FT-IR, FESEM, TEM, zeta potential measurement and elemental mapping. Microscopic image showed that MnFe2O4 is in cluster form composed from tiny nanoparticles. After saccharide functionalization hybrid composite generate hyper-crosslinked porous structure as a result of polysilicate formation due to hydrolysis of silica source. Escherichia coli and bacillus subtilis were selected as sample pathogens to evaluate the bacteria capturing ability of the magnetic glycopolymer. At the optimum conditions (pH = 6, time of 20 min, dosage of 15 mg) removal efficiency was more than 99% using both saccharide.

Colorimetric aptasensor for Campylobacter jejuni cells by exploiting the peroxidase like activity of Au@Pd nanoparticles.

The authors describe a method for colorimetric determination of Campylobacter jejuni (C. jejuni) in milk samples. It is based on the interaction of a specific DNA aptamer with surface protein in the cell membranes of C. jejuni. Specific binding of the aptamer with the cell membrane leads to an uptake of aptamer from solution. As a result, the concentration of aptamer floating in the solution is reduced. In the presence of large quantities of aptamer, the surface of added Au@Pd nanoparticles (NPs) is covered with aptamer via electrostatic interactions. Hence, they cannot act as a peroxidase mimic and oxidize the substrate 3,3',5,5'-tetramethylbenzidine (TMB) to give a blue product. However, when the aptamer is bound by the target cells, the surface of the NPs is not blocked by aptamer and the NPs exert a strong peroxidase -like activity. Under defined experimental conditions, the intensity of the blue color increases with the concentration of C. jejuni, and as little as 100 CFU·mL-1 can bedetected in milk. Graphical abstract A colorimetric aptasensor for assay Campylobacter jejuni whole cell in food samples was investigated. This assay was designed based on interaction of specific DNA aptamer with surface protein in c. jejuni cell membrane without any modification of aptamer.

A Novel Label-Free microRNA-155 Detection on the Basis of Fluorescent Silver Nanoclusters.

In this paper, a new approach for microRNA-155 (miRNA-155) detection was described based on the fluorescence quenching of oligonucleotide-templated silver nanoclusters (DNA-AgNCs). The specific DNA scaffold with two different nucleotides fragments were used: one was enriched with a cytosine sequence fragment (C12) that could result in DNA-AgNCs with a high quantum yield via a chemical reduction method, and the other was the probe fragment (5- CUGUUAAUGCUAAUCGUG-3) which could selectively bind to the miRNA-155. Thus, the as-prepared AgNCs could exhibit quenched fluorescence when binding to the target miRNA-155. The fluorescence ratio of the DNA-AgNCs was quenched in a linearly proportional manner to the concentration of the target in the range of 0.2 nM to 30 nM with a detection limit of 0.1 nM.

Development of 177Lu-Cetuximab-PAMAM dendrimeric nanosystem: a novel theranostic radioimmunoconjugate.

PURPOSE: Epidermal growth factor receptors (EGFRs) are overexpressed in a wide range of tumors and are attractive candidates to target in targeted therapies. This study aimed to introduce a novel radiolabeled compound, 177Lu-cetuximab-PAMAM G4, for the treatment of EGFR-expressing tumors. METHODS: In this study, the cetuximab mAb was bound to PAMAM G4 and labeled with 177Lu via DTPA-CHX chelator. The synthesized nanosystem was confirmed by different analyses such as DLS, FT-IR, TEM, and RT-LC. Cell viability of the radioimmunoconjugate was assessed over the EGFR-expressing cell line of SW480. The biodistribution of 177Lu-Cetuximab-PAMAMG4 was determined in different intervals after injection of the radiolabeled compound in normal and tumoral nude mice via scarification and SPECT images. RESULTS: The average size of PAMAM G4 and PAMAM-Cetuximab-DTPA-CHX nanoparticles were 2 and 70 nm, respectively. 177Lu-Cetuximab-PAMAMG4 was prepared with radiochemical purity of more than 98%. The survival rates of SW480 cells at 24, 48, and 72 h post-treatment with177Lu-Cetuximab-PAMAMG4 (500 nM) were 18%, 15%, and 14%, respectively. The biodistribution studies showed a significant accumulation of 177Lu-Cetuximab-PAMAM in the EGFR-expressing tumor. CONCLUSION: According to the results, this new agent can be considered as an efficient therapeutic complex for tumors expressing EGFR receptors.

Fabrication and evaluation of optical nanobiosensor based on localized surface plasmon resonance (LSPR) of gold nanorod for detection of CRP.

C-reactive protein (CRP) is a plasma protein that is one of the most expressed proteins in acute phase inflammation cases. It is a well-known biomarker for inflammatory disorders. There is a significant correlation between increasing CRP concentration and the risk of being exposed to cardiovascular diseases (CVD) and sepsis; thus, monitoring and quantifying CRP levels in a simple, inexpensive, and quick manner can improve clinical diagnostics and help prevent major inflammatory conditions. Here a nanobiosensor was developed, benefiting from the LSPR property of gold-nanorod (GNR) to measure CRP concentration. Nanorods were fabricated using One-pot synthesis by trimethyl ammonium bromide (CTAB) as a surfactant. This method provides the advantage of both step and time reduction in synthesis and decreases the contamination probability of nanorods as the products. The nanorods were characterized using TEM with an average size of (24 ± 1 nm) × (5 ± 1 nm) and a typical aspect ratio of ∼4.9. The surface of the rods was modified with a specific aptamer for the target protein, and the LSPR shifts due to the gold nanorod's refractive index change as the result of protein interaction with the biosensor investigated using a 100-900 nm UV absorption device. The results indicated that the nanobiosensor could respond to different CRP concentrations within 30 min. The selectivity test has shown nonresponsive results of nanobiosensor to BSA and TNF-α proteins which are used to evaluate the biosensor behavior in non-target proteins. The detection limit was evaluated at 2 nM, and the sensor's linear response ranged between 2 - 20 nM.

Chromone-embedded peptidomimetics and furopyrimidines as highly potent SARS-CoV-2 infection inhibitors: docking and MD simulation study.

BACKGROUND: COVID-19 is a respiratory illness caused by SARS-CoV-2. Pharmaceutical companies aim to control virus spread through effective drugs. This study investigates chromone compound derivatives' ability to inhibit viral entry and prevent replication. METHOD: This study investigated the inhibitory effect of chromone-embedded peptidomimetics and furopyrimidines on 7BZ5 from Severe Acute Respiratory Syndrome CoV-2, Homo sapiens, and 6LU7 from Bat SARS-like CoV using molecular docking. The crystal structure of these proteins was obtained from the Protein Data Bank, and the inhibition site was determined using ligand binding interaction options. The 3D structure was protonated and energetically minimised using MOE software. Chromone derivatives were designed in three dimensions, and their energy was minimised using MOE 2019. The molecular drug-likeness was calculated using SwissADME, Lipinski and Benigni-Bossa's rule, and toxicity was calculated using Toxtree v3.1.0 software. Compounds with pharmacological properties were selected for molecular docking, and interactions were assessed using MOE 2019. MD simulations of Mpro-ch-p complexes were performed to evaluate root mean square fluctuations (RMSF) and measure protein stability. RESULT: The pharmacokinetic tests revealed that chromone derivatives of the peptidomimetic family have acceptable pharmacokinetic activity in the human body. Some compounds, such as Ch-p1, Ch-p2, Ch-p6, Ch-p7, Ch-p12, and Ch-p13, have pronounced medicinal properties. Molecular docking revealed high affinity for binding to SARS-CoV-2 protease. Ch-p7 had the highest binding energy, likely due to its inhibitory property. A 10 ns molecular dynamics study confirmed the stability of the protein-ligand complex, resulting in minimal fluctuations in the system's backbone. The MM-GBSA analysis revealed free energies of binding of - 19.54 kcal/mol. CONCLUSIONS: The study investigated the inhibition of viral replication using chromone derivatives, finding high inhibitory effects in the peptidomimetic family compared to other studies.

(E)-1-(2-Nitro-benzyl-idene)-4-phenyl-thio-semicarbazide.

In the title mol-ecule, C(14)H(12)N(4)O(2)S, the conformation about the imine bond is trans. The dihedral angle between the two rings is 88.22 (11)°. An intra-molecular N-H⋯N contact occurs. The crystal structure features N-H⋯S and C-H⋯O hydrogen bonds.

Synthesis and biological evaluation of propargyl acetate derivatives as anti-mycobacterial agents.

BACKGROUND: The emergence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb) has intensified efforts to discover novel drugs for tuberculosis (TB) treatment. Targeting the persistent state of Mtb, a condition in which Mtb is resistant to conventional drug therapies, is of particular interest. METHODS: This study is focused on propargyl acetate derivatives. Eight molecules were designed based on propargyl alcohols and different acid anhydrides. RESULTS: All the synthesized compounds and commercially available ones were evaluated for anti-tuberculosis activity. CONCLUSIONS: Inhibitors against Mtb have been identified and characterized for further development into potential novel anti-tubercular drugs.

Buried-Gate MWCNT FET-Based Nanobiosensing Device for Real-Time Detection of CRP.

C-reactive protein (CRP), an acute-phase protein synthesized in the liver in response to inflammation, is one of the biomarkers used for the detection of several diseases. Sepsis and cardiovascular diseases are two of the most important diseases for which detection of CRP at very early stages in the clinical range can help avert serious consequences. Here, a CNT-based nanobiosensing system, which is portable and reproducible, is used for label-free, online detection of CRP. The system consists of an aptameric CNT-based field-effect transistor benefiting from a buried gate geometry with Al2O3 as a high dielectric layer and can reflect the pro-cytokine concentration. Test results show that the device responds to CRP changes within 8 min, with a limit of detection as low as 150 pM (0.017 mg L-1). The device was found to have a linear behavior in the range of 0.43-42.86 nM (0.05-5 mg L-1). The selectivity of the device was tested with TNF-α, IL-6, and BSA, to which the nanosensing system showed no significant response compared with CRP. The device showed good stability for 14 days and was completely reproducible during this period. These findings indicate that the proposed portable system is a potential candidate for CRP measurements in the clinical range.

Recent progress of isocyanide-based multicomponent reactions in Iran.

The aim of this review is to provide an overview of the contributions and recent advances made by Iranian scientists in the field of isocyanide-based reactions between 1999 and 2009. With over 100 publications during this period, Iranians are responsible for approximately 10% of all publications in the world involving isocyanide-based multicomponent reactions (IMCRs). Some important aspects of these IMCRs include the execution of reactions in green reaction mediums like water or ethanol, high atom economies, mild reaction conditions, high yields, and catalyst-free processes. On the other hand, in most of these reactions, new classes of heterocyclic compounds with potential biological and medicinal activities have been reported.

In vitro and in vivo evaluation of a nanofiber wound dressing loaded with melatonin.

Wound healing is a complicated process that takes a long time to complete. The three-layer nanofiber wound dressing containing melatonin is highly expected to show remarkable wound repair by reducing the wound healing time. In this study, chitosan (Cs)-polycaprolactone (PCL)/ polyvinylalcohol (PVA)-melatonin (MEL)/ chitosan-polycaprolactone three-layer nanofiber wound dressing was prepared by electrospinning for melatonin sustained release. The characteristics of the wound dressing were further evaluated. The wound dressing had a high water uptake after 24 h (401%), and the water contact angle results showed that it had hydrophilicity effect that supported the cell attachment. The wound healing effect of wound dressing was examined using a full-thickness excisional model of rat skin by the local administration of MEL. The gene expressions of transforming growth factor-beta (TGF-ß1), alpha-smooth muscle actin (α-SMA), collagen type I (COL1A1), and collagen type III (COL3A1) were further studied. The histopathological evaluation showed the complete regeneration of the epithelial layer, remodeling of wounds, collagen synthesis, and reduction in inflammatory cells. The NF + 20% MEL significantly increased TGF-ß1, COL1A1, COL3A1, and α-SMA mRNA expressions. This wound dressing may have a considerable potential as a wound dressing to accelerate the wound healing.

Pyridine-functionalized MCM-41 as an efficient and recoverable catalyst for the synthesis of pyran annulated heterocyclic systems.

Pyridine-functionalized MCM-41 catalyzed reactions between tetracyanoethylene and various activated CH-acid compounds are described. These reactions afford the corresponding pyran annulated heterocyclic ring systems in high yields at room temperature within a few minutes. The work-up procedure is very simple and the products do not require further purification. The catalyst can be recycled and reused for several times without observable loss of performance.

A lectin-coupled porous silicon-based biosensor: label-free optical detection of bacteria in a real-time mode.

Accuracy and speed of detection, along with technical and instrumental simplicity, are indispensable for the bacterial detection methods. Porous silicon (PSi) has unique optical and chemical properties which makes it a good candidate for biosensing applications. On the other hand, lectins have specific carbohydrate-binding properties and are inexpensive compared to popular antibodies. We propose a lectin-conjugated PSi-based biosensor for label-free and real-time detection of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by reflectometric interference Fourier transform spectroscopy (RIFTS). We modified meso-PSiO2 (10-40 nm pore diameter) with three lectins of ConA (Concanavalin A), WGA (Wheat Germ Agglutinin), and UEA (Ulex europaeus agglutinin) with various carbohydrate specificities, as bioreceptor. The results showed that ConA and WGA have the highest binding affinity for E. coli and S. aureus respectively and hence can effectively detect them. This was confirmed by 6.8% and 7.8% decrease in peak amplitude of fast Fourier transform (FFT) spectra (at 105 cells mL-1 concentration). A limit of detection (LOD) of about 103 cells mL-1 and a linear response range of 103 to 105 cells mL-1 were observed for both ConA-E. coli and WGA-S. aureus interaction platforms that are comparable to the other reports in the literature. Dissimilar response patterns among lectins can be attributed to the different bacterial cell wall structures. Further assessments were carried out by applying the biosensor for the detection of Klebsiella aerogenes and Bacillus subtilis bacteria. The overall obtained results reinforced the conjecture that the WGA and ConA have a stronger interaction with Gram-positive and Gram-negative bacteria, respectively. Therefore, it seems that specific lectins can be suggested for bacterial Gram-typing or even serotyping. These observations were confirmed by the principal component analysis (PCA) model.

Development of chitosan-coated liposome for pulmonary delivery of N-acetylcysteine.

The purpose of the present investigation was to formulate NAC (N-acetylcysteine)-loaded chitosan (CH)-coated liposome aiming at obtaining an effective formulation able to ensure a prolonged and controlled release of NAC to the lung by inhalation. Empty liposomes [(DPPG/Chol/DPPG with different molar percentages of DPPG) (0, 1, 2.5, 5)] were prepared and coated with CH at different CH/Lipid ratio (0.5, 1, 1.5,2, 2.5, W/W) to reach optimum coating of CH. TEM and SEM indicated that morphology of CH-coated and -uncoated liposomes were spherical. FTIR analysis indicated attachment of CH on liposome surface. The drug release experiment in the simulated lung fluid showed that the CH-uncoated and -coated liposomes released 51% and 38% of NAC during 9 h, respectively. The results showed that coating of liposome with CH resulted in the prolonged release of NAC from CH-coated liposome. The results of flow cytometry indicated the effective uptake of CH-coated liposome compared with the CH-uncoated liposome in epithelial cells. In vivo experiment indicated good deposition and retention of CH-coated liposome in lung in comparison with CH-uncoated liposome. The results of the present study demonstrated that CH-coated liposome may represent a promising carrier for the delivery of NAC to the lungs by inhalation therapy.

Whole cell FRET immunosensor based on graphene oxide and graphene dot for Campylobacter jejuni detection.

In this work a new fluorescence immunosensor with use of graphene oxide and graphene quantum dot for detection Campylobacter jejuni whole cell in food samples was designed. This biosensor was designed based on interaction of poly clonal antibody conjugated with graphene quantum dot with surface protein in Campylobacter jejuni cell membrane. Specific binding of graphene quantum dot with Campylobacter jejuni membrane leads to generate a distance among graphene dot and graphene oxide and fluorescence is ON. In lack of Campylobacter jejuni or in existence of other bacterial cells, distance between of graphene dot and graphene oxide is very low and graphene quantum dot fluorescence emission was OFF. Experiment revealed that step by step increase in bacterial target cells caused to gradually increased fluorescence emission and this process was linear. Limit of detection for this bacterial sensor was 10 CFU/ml and ability of this FRET immunosensor for Campylobacter jejuni sensing in comparison with other bacterial cells was significant. Also, this method for monitoring Campylobacter jejuni in poultry liver was applied and results revealed that this immunosensor could be used for analysis bacterial cell in food samples.

Controlled Tyrosine Kinase Inhibitor Delivery to Liver Cancer Cells by Gate-Capped Mesoporous Silica Nanoparticles.

Hepatocellular carcinoma is the most common type of primary malignancy in the liver and one of the most common types of cancer worldwide. Its readily increasing mortality rate highlights the urgent need for the development of efficient therapeutic strategies. Tyrosine kinase inhibitors (TKIs) such as sorafenib and sunitinib are used as efficient angiogenesis inhibitors for this purpose. However, despite their pharmacological effects, their transfer into clinical practice is characterized by their poor aqueous solubility and accumulation in off-target tissues, resulting in unfavorable side effects. Here, we report a nanocomposite made of amine-functionalized mesoporous silica nanocomposites (MSNs) that are surface-coated with cerium oxide nanoparticles (CNPs) for the controlled delivery and release of TKIs. Amine-functionalized MSNs were prepared using a sol-gel method and loaded with TKIs. To trap drug molecules into the mesoporous structure, CNPs were covalently conjugated to the surface of MSNs. The synthesis and functionalization steps were controlled using different characterization methods, confirming the desired morphology and structure, the identity of functional groups on the surface, successful coating, and appropriate loading efficiency. Under physiological conditions, CNP-capped MSNs demonstrated a sustained drug release over time as a result of CNPs' gatekeeping effect on the payloads. Strong cellular interactions with different liver cancer cells and enhanced cellular uptake were also observed in vitro for the gate-capped MSNs. Internalization of nanocomposites induced cell death via the production of reactive oxygen species, and subsequent activation of apoptosis pathways. This study demonstrates that gate-capped MSNs are promising chemotherapeutic vehicles characterized by a sustained drug release profile and high cellular internalization.