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Integrating imaging and therapeutic capabilities into a single entity can offer enhanced diagnostic accuracy and treatment efficacy in clinically effective formulations. Due to the diversity of chemical structures and/or limited solubility of inhibitors or fluorophores, it is essential to employ a robust delivery carrier that can facilitate drug absorption and distribution during its circulation in the blood. This study explores the potential of hollow gadolinium oxide (Gd2O3) nanocarriers in imaging and drug delivery applications. The citric acid (CA)-capped hollow gadolinium oxide nanocarriers were synthesized via urea-assisted precipitation and hydrothermal methods using carbon spheres as sacrificial templates. The resulting nanosized hollow spheres displayed a spherical morphology and demonstrated relaxation rates in the longitudinal and transverse directions, as indicated by their r 1 and r(2) values of 1.8 and 5.3 s(-1) mM(-1), respectively. To mimic the physiological conditions, the hollow gadolinium oxide spheres were loaded separately with antibiotic sparfloxacin and the azo dye Congo red at neutral pH (7.4) and body temperature (37 degrees C). The CR-loaded nanospheres exhibited a time-dependent internalization behavior with HeLa cells, suggesting their imaging potential for intracellular drug delivery. Furthermore, the SP-loaded nanospheres demonstrated antimicrobial activity against both Gram-positive and Gram-negative bacteria, demonstrating their therapeutic potential against bacterial infections. To mitigate the risk of leaching of Gd3+ ions and their inherent toxicity, a CA coating was applied to hollow gadolinium oxide surface which resulted in outstanding cell viability of the surface functionalized nanocarriers. In addition, the CA coating offered additional support for the increased encapsulation and continuous release of drug molecules until 1 week (168 h). The characterization data provide evidence for the potential of CA-capped hollow gadolini, Funding Agencies|Deutscher Akademischer Austauschdienst; University of Cologne within the framework of UoC-Forum; Advanced Concepts for Therapy and Diagnostic; German Academic Exchange Service (DAAD)

Correction for 'Click functionalized biocompatible gadolinium oxide core-shell nanocarriers for imaging of breast cancer cells' by Shifaa M. Siribbal et al., RSC Adv., 2022, 12, 31830-31845, https://doi.org/10.1039/D2RA00347C.

Site-specific delivery using functionalized nanocarriers is in high demand in imaging applications of modern clinical research. To improve the imaging capabilities of conventionally used contrast agents and expand the targeting accuracy, functional gadolinium oxide based nanocarriers originated from homogeneous core shells structures (Gd2O3@SiO2@Fe3O4) were developed using a multilayer formation approach. The synthesis and chemical configuration for the covalent binding of macrocyclic chelating agents and estrogen targeting molecules on these nanocarriers were designed by a two-step chemical synthesis method. Initially, SiO2@Fe3O4 structures were prepared and encapsulated with a homogenous thin Gd2O3 overlayer. The exterior surface of the as-prepared carriers offered chemical binding with a breast cancer specific estrogen molecule, covalently grafted through a Click-Chemistry protocol. In the next step, to enhance the diagnostic imaging capabilities of these carriers, thiocyanate-linked chelator molecule, DOTA, was attached to the surface of estrogen bound Gd2O3@SiO2@Fe3O4 using basic reaction conditions. The active amino groups before and after conjugation of estrogen molecules on the surface were quantified using a fluorescamine based approach. Due to the covalent binding of the macrocyclic chelator to the Gd2O3@SiO2@Fe3O4 surface, core shell carriers showed potential radiolabeling efficiency using positron emitter radionuclide, gallium-68 (Ga-68). Intracellular uptake of estrogen-conjugated carriers was evaluated with MCF7 breast cancer cell lines using confocal laser scanning microscopy and fluorescent flow cytometry. In addition, in vitro cytotoxicity studies of functional nanocarriers as compared to bare nanoparticles showed reduced toxicity to HEK-293 cells demonstrating the role of surface attached molecules in preventing direct exposure of the Gd2O3 surface to the cells. The as-developed gadolinium based nanocarriers presented excellent capabilities as bioc

To date, there are no preoperative and quantitative dynamics in clinical practice that can reliably differentiate between a benign and malignant renal cell carcinoma (RCC). For monitoring different analytes in body fluids, more than 40 different molecular biomarkers have been identified, however, they are associated with limited clinical sensitivity and/or non-optimal specificity due to their leaky nature. Previous work on RCC demonstrated the miRNA15a to be reliable and novel biomarker with 98.1% specificity and 100% sensitivity. Despite the high potential of miRNA15a biomarker, its clinical application is considerably hampered by the insensitive nature of the detection methods and low concentration of biomarker in samples that is aggravated by the high level of contamination due to other solutes present in body fluids. In this work, a non-invasive quantitative approach is demonstrated to overcome such diagnostics issues through biotin-streptavidin binding and fluorescence active magnetic nanocarriers that ensured prompt isolation, enrichment and purification of the biomarker miRNA15a from urine. The study demonstrates that detectable low levels of these miRNAs through miRNA capturing nanocarriers can potentially function as advanced diagnostic markers for the non-invasive investigation and early detection of renal cancer.

Zinc oxide (ZnO) nanoparticles (NPs), which are declared as generally recognized as safe by the U.S. Food and Drug Administration, is discussed in this review to reveal their beneficial characteristics when incorporated into packaging matrixes for food packaging and preservation applications. Some of the major challenges in conventional packaging include microbial contamination, oxidation, moisture, gas, and UV transmission into the food, and lack of mechanical strength. These factors lead to poor shelf life, affect food quality, and cause food wastage. Advancement in packaging has shifted the focus toward nanotechnology. Nanotechnology is oriented toward the fabrication and application of materials with nanosized dimensions. Among various nanomaterials, current research has focused on ZnO NPs due to their properties and future applications. Incorporation of ZnO NPs into biopolymer packaging materials considerably enhanced the antimicrobial activity against foodborne pathogens and prolonged the shelf life of foodstuffs by a Trojan-horse strategy and reactive oxygen mechanism. Besides antimicrobial activity, ZnO NPs allow improvement of the antioxidant activity of the packaging materials by limiting the presence of oxygen in the headspace. Comprehensive ZnO nanocomposite (NC) biopolymer (BP) packaging features and their significance for food packaging applications are presented in this review. Furthermore, it discusses the effect of ZnO NPs on mechanical strength and barrier properties such as water vapor permeability, oxygen transmission rate, and UV transmission across the packaging material.

Surface modification of nanocarriers enables selective attachment to specific molecular targets within a complex biological environment. Besides the enhanced uptake due to specific interactions, the surface ligands can be utilized for radiolabeling applications for bimodal imaging ensured by positron emission topography (PET) and magnetic resonance imaging (MRI) functions in one source. Herein, we describe the surface functionalization of magnetite (Fe3O4) with folic acid as a target vector. Additionally, the magnetic nanocarriers were conjugated with appropriate ligands for subsequent copper-catalyzed azide-alkyne cycloaddition or carbodiimide coupling reactions to successfully achieve radiolabeling with the PET-emitter F-18. The phase composition (XRD) and size analysis (TEM) confirmed the formation of Fe3O4 nanoparticles (6.82 nm +/- 0.52 nm). The quantification of various surface functionalities was performed by Fourier-transform infrared spectroscopy (FT-IR) and ultraviolet-visible microscopy (UV-Vis). An innovative magnetic-HPLC method was developed in this work for the determination of the radiochemical yield of the F-18-labeled NPs. The as-prepared Fe3O4 particles demonstrated high radiochemical yields and showed high cellular uptake in a folate receptor overexpressing MCF-7 cell line, validating bimodal imaging chemical design and a magnetic HPLC system. This novel approach, combining folic acid-capped Fe3O4 nanocarriers as a targeting vector with F-18 labeling, is promising to apply this probe for bimodal PET/MR-studies.

Recognition of folate and biotin surface receptors by dual-functionalized nanoparticles (NPs) is key for site-selective receptor-mediated transport of anticancer drugs to cancer cells. We present here dopamine-capped iron oxide nanoprobes (Fe3O4, 10 +/- 2 nm) containing two surface-grafted biologically relevant ligands, namely, folic acid (FA) and biotin (BT). The covalent attachment of both FA and BT on Fe3O4 nanoparticles was achieved by following carbodiimide coupling and click-chemistry protocols. The dual-function Fe 3 0 4 probes were delivered into E-G7 and human HeLa cancer cell lines and tested toward their cellular uptake by immunofluorescence and flow cytometry analysis. Owing to receptor-mediated endocytosis, enhanced accumulation of nanoprobes in cancer cells was successfully monitored by confocal laser microscopy. When compared to dual-function probes, single-functionalized nanoparticles possessing either FA or BT ligands showed significantly reduced uptake in the tested cell lines, underlining the superior interaction potential of dual-purpose probes. A time-dependent receptor-mediated endocytosis of FA-Fe3O4-BT nanovectors was demonstrated by flow cytometry analysis, whereas the unfunctionalized NPs did not show any specificity in terms of uptake. Besides their specific uptake, the surface-functionalized nanoparticles exhibited promising cytotoxicity profiles by demonstrating good viability of more than 95% with analogous cancer cell lines. Our results demonstrate that dual and/or multivariate conjugation of receptor-specific ligands on NPs is highly effective in molecular recognition of surface biomarkers that enhances their potential in anticancer treatment for pretargeting-radio strategies based on biotin/avidin interactions.

Iron oxide nanoparticles (NPs) are extensively used in various biomedical applications due to their suitability as carriers of diagnostic and therapeutic agents. Herein, we report on the evaluation of concentration-dependent toxicity studies of iron oxide (magnetite) NPs in zebrafish (Danio rerio). To follow the update of iron oxide NPs in the animal model, particles were functionalized by conjugating a fluorescent dye (Congo red) that serves as an efficient probe to track the uptake and accumulations of nanoparticles from the early life stages of zebrafish. As in vivo model organism to study the diffusion an in vivo toxicity, zebrafish embryos and larvae were treated with different concentrations of CR@Fe3O4 conjugates (100-800 mu g/mL) for 4-96 h postfertilization (hpf). Monitoring of mortality, hatching rate, and whole-embryo cellular death showed that incubation of low concentrations of the NPs did not exhibit adverse developmental toxicity during embryonic and larval stages of zebrafish. Minimal toxic effects were observed at high concentration (800 mu g/mL) of CR@Fe3O4, causing mortality and delay in hatching cycles. However, CR@Fe3O4 exhibited higher toxic effect on zebrafish larvae, suggesting higher bioavailability of the NPs on the tested animal stage. This study provides an investigation on developmental toxicity in zebrafish caused by Fe3O4 NPs and provides innovative insight into CR@Fe3O4 NPs serving as an optical probe to study the potential nanotoxicological effects of NPs in in vivo systems.

We demonstrate here a controlled assembly of individual nanoscale building blocks into defined architectures based on chemospecific covalent bonding interactions. For this purpose, alpha-Fe2O3, gamma-Fe2O3, and SiO2 nanoparticles decorated with surface-conjugated organic ligands were used for performing on-surface Diets-Alder reactions. Driven through their chemical affinity and surface-grafted complementary functionalities, nanoparticles underwent click-reactions to produce covalently organized nanostructures. An advantage of using the Diels-Alder reaction is its reversible nature, which was used to click and unclick the nanoparticles on demand. The efficiency and chemical specificity of this approach opens up another synthetic access to unify materials with complementary properties, where the thermoresponsive nature of particle assemblies imparts to them a fully reversible character. The covalent conjugation strategies demonstrated in this work potentially allow the use of a diverse range of particles and ligands for their applications in different disciplines such as medicine, optics, or photonics. The nanoparticles morphology and crystalline nature were investigated by TEM and XRD analysis, while the presence of surface attached groups was verified by NMR, FTIR, UV-vis, and potential measurements.

Combining individual nanoparticles (NPs) of different chemical composition and surface chemistry offers an unexplored synthetic avenue for unifying different functionalities into a topologically defined hybrid structure. In this study, multiparticle architectures (alpha-Fe2O3@SiO2, alpha-Fe2O3@gamma-Fe2O3) were fabricated by a directed self-assembly of nanoparticles carrying complementary surface ligands suitable for click chemistry. For this purpose, the surface-rooted hydroxyl groups of freshly prepared alpha-Fe2O, gamma-Fe2O3, and SiO2 nanoparticles were utilized for facile conjugation of organic ligands, 4-(azidoacetyl)-catechol, and 10-undecynoic acid to subsequently perform copper catalyzed reactions. This work explores specific chemical interactions among functionalized nanopartides of different sizes and compositions to create nanoparticle assemblies with hybrid topologies. Here, developed on-surface chemistry protocols demonstrate that chemical specificity known for dick-chemistry protocols among molecular species is equally effective between the ligands grafted on the surface of nanoparticles. Owing to the presence of active ligands and their mutual binding affinities, architectures of nanoparticles with a high degree of symmetry and notable magnetic properties were obtained. The exterior of the nanoassembly presents active surface groups for further functionalization and attachment of modality such as the dual-mode magnetic resonance imaging. The morphology and crystalline nature of the NPs were investigated by transmission electron microscopy and X-ray diffraction analysis, whereas the active nature of the surface attached groups was determined by NMR, Fourier transform infrared, UV-vis, and zeta-potential measurements.

Efficient therapies for breast cancer remain elusive because of the lack of strategies for targeted transport and receptor-mediated uptake of synthetic drug molecules by cancer cells. Conjugation of nanoparticles (NPs) with active targeting ligands enabling selective molecular recognition of antigens expressed on the surface of cancer cells is promising for localization and treatment of malignant cells. In this study, covalent attachment of synthetic estrogen 17 alpha-ethynylestradiol on the silica (SiO2) shell of silica-gold NPs (SiO2@Au) was undertaken to improve the cancer-targeting ability of the nano-biotags. Chemical and structural analysis of the bioconjugates examined in solution (UV-vis and xi-potential) and solid state (Fourier transform infrared spectroscopy, X-ray diffractometry, and transmission electron microscopy) confirmed the identity of the carrier particles and surface-bound ligands. The mesoporous silica shell served as a reservoir for anticancer drugs (doxorubicin and quercetin) and to facilitate covalent attachment of receptor molecules by click chemistry protocols. The chemoselective recognition between the nanoconjugates and cell membranes was successfully demonstrated by the accumulation of nanoprobes in the tumor tissue of mice with subcutaneous breast cancer, whereas healthy cells were unaffected. The drug release studies showed sustained release kinetics over several weeks. These findings elaborate the exceptional selectivity and potential of estrogen-coated nano-biolabels in efficient diagnosis and detection of breast cancer cells.

Hollow mesoporous silica capsules (HMSC) are potential drug transport vehicles due to their biocompatibility, high loading capacity and sufficient stability in biological milieu. Herein, we report the synthesis of ellipsoid-shaped HMSC (aspect ratio approximate to 2) performed using hematite particles as solid templates that were coated with a conformal silica shell through cross-condensation reactions. For obtaining hollow silica capsules, the iron oxide core was removed by acidic leaching. Gas sorption studies on HMSC revealed mesoscopic pores (main pore width approximate to 38 angstrom) and a high surface area of 308.8 m(2) g(-1). Cell uptake of dye-labeled HMSC was confirmed by incubating them with human cervical cancer (HeLa) cells and analyzing the internalization through confocal microscopy. The amphiphilic nature of HMSC for drug delivery applications was tested by loading antibiotic (ciprofloxacin) and anticancer (curcumin) compounds as model drugs for hydrophilic and hydrophobic therapeutics, respectively. The versatility of HMSC in transporting hydrophilic as well as hydrophobic drugs and a pH dependent drug release over several days under physiological conditions was demonstrated in both cases by UV-vis spectroscopy. Ciprofloxacin-loaded HMSC were additionally evaluated towards Gram negative (E. coli) bacteria and demonstrated their efficacy even at low concentrations (10 g ml(-1)) in inhibiting complete bacterial growth over 18 hours.

Using metal organic precursors in materials synthesis remains a challenge due to their high moisture susceptibility. In this work, we describe a facile methodology for the synthesis of Gd2O3-based contrast agents from two new gadolinium-based complexes. [Gd(PyTFP)(4)] (PyH) 1 (PyTFP = C8H5NOF3, Py = C5H5N) and [Gd(DMOTFP)(3)Py] 2 (DMOTFP = C8H7NO2F3) were synthesized via a classical ligand exchange reaction of [Gd{N(SiMe3)(2)}(3)] under inert conditions. As a result, X-ray diffraction analysis revealed a distorted square antiprismatic coordination and an augmented triangular prismatic arrangement of ligands around gadolinium atoms in 1 and 2, respectively. It also showed that 1 is an anionic complex of formula [Gd(PyTFP)(4)](PyH), while a neutral tris-compound, [Gd(DMOTFP)(3)Py], was obtained as a pyridine adduct in 2. Fast and reproducible microwave-assisted decomposition of 1 and 2 provided homogeneous Gd(OH)(3) nanorods at mild temperature without using any surfactant or capping reagent. As-synthesized nanorods were easily transformed into a cubic phase of Gd2O3 nanoparticles by thermal treatment under ambient conditions. The magnetic measurement showed the typical paramagnetic behavior of the Gd2O3 nanoparticles (NPs). The cytotoxicity profile demonstrates the biocompatibility and negligible toxicity of the as-synthesized nanoprobes. The suggested approach provides a new class of gadolinium-based precursors which allows facile synthesis of highly crystalline Gd2O3 NPs.

A facile bottom-up approach for the synthesis of inorganic/organic bioconjugated nanoprobes based on iron oxide nanocubes as the core with a nanometric silica shell is demonstrated. Surface coating and functionalization protocols developed in this work offered good control over the shell thickness (840 nm) and enabled biovectorization of SiO2@Fe3O4 coreshell structures by covalent attachment of folic acid (FA) as a targeting unit for cellular uptake. The successful immobilization of folic acid was investigated both quantitatively (TGA, EA, XPS) and qualitatively (AT-IR, UVvis, zeta-potential). Additionally, the magnetic behavior of the nanocomposites was monitored after each functionalization step. Cell viability studies confirmed low cytotoxicity of FA@SiO2@Fe3O4 conjugates, which makes them promising nanoprobes for targeted internalization by cells and their imaging.

Superparamagnetic iron oxide nanoparticles (SPIONs) coated with azide groups were functionalized at the surface with biotin (biotin@SPIONs) and cysteine protease inhibitor E-64 (E-64@SPION5) with the purpose of developing nanoparticle-based assays for identifying cysteine proteases in proteomes. Magnetite particles (ca. 6 nm) were synthesized by microwave-assisted thermal decomposition of iron acetylacetonate and subsequently functionalized following a click chemistry protocol to obtain biotin and E-64 labeled particulate systems. Successful surface modification and covalent attachment of functional groups and molecules were confirmed by FT-IR spectroscopy and thermal gravimetric analysis. The ability of the surface-grafted biotin terminal groups to specifically interact with streptavidin (either horseradish peroxidase [(HRP)-luminol-H2O2] or rhodamine) was confirmed by chemiluminescent assay. A quantitative assessment showed a capture limit of 0.55-1.65 mu g protein/100 mu g particles. Furthermore, E-64@SPION5 were successfully used to specifically label papain-like cysteine proteases from crude plant extracts. Owing to the simplicity and versatility of the technique, together with the superparamagnetic behavior of FeOx-nanoparticles, the results demonstrate that click chemistry on surface anchored azide group is a viable approach toward bioconjugations that can be extended to other nanoparticles surfaces with different functional groups to target specific therapeutic and diagnostic applications.