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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 (Gd 2 O 3 @SiO 2 @Fe 3 O 4 ) 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, SiO 2 @Fe 3 O 4 structures were prepared and encapsulated with a homogenous thin Gd 2 O 3 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 Gd 2 O 3 @SiO 2 @Fe 3 O 4 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 Gd 2 O 3 @SiO 2 @Fe 3 O 4 surface, core shell carriers showed potential radiolabeling efficiency using positron emitter radionuclide, gallium-68 ( 68 Ga). 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 Gd 2 O 3 surface to the cells. The as-developed gadolinium based nanocarriers presented excellent capabilities as biocompatible target-specific imaging probes which indicates great potential in the field of dual-mode contrast agents., Competing Interests: The authors declare no competing financial conflict of interest., (This journal is © The Royal Society of Chemistry.)

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.

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 (Fe 3 O 4 ) 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 18 F. The phase composition (XRD) and size analysis (TEM) confirmed the formation of Fe 3 O 4 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 18 F-labeled NPs. The as-prepared Fe 3 O 4 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 Fe 3 O 4 nanocarriers as a targeting vector with 18 F labeling, is promising to apply this probe for bimodal PET/MR-studies.

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 17α-ethynylestradiol on the silica (SiO 2 ) shell of silica-gold NPs (SiO 2 @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 ξ-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.

There is evidence of an association between childhood maltreatment and lifelong cognitive impairment. Few studies investigate cognitive functioning in maltreated children. The objective of this study was to investigate whether there are differences in executive processing between maltreated and nonmaltreated children. Additionally, clinical symptoms were compared between groups and possible associations between clinical symptoms, and deficits in executive functions were investigated. The sample consisted of 55 children (8-12 years), 30 with a history of maltreatment and 25 with no history of maltreatment. An interview was conducted with the child's legal guardian and instruments were administered: Juvenile Victimization Questionnaire (JVQ), Child Behavior Checklist (CBCL), and Spence Children's Anxiety Scale (SCAS). The following clinical instruments were administered to the children: JVQ, Trauma Symptom Checklist for Children (TSCC), and Children's Depression Inventory (CDI). Children underwent neuropsychological assessment. Data were analyzed by comparing the groups for clinical and cognitive variables. Differences were found between the groups in all executive functions. Most clinical symptomatology scales showed differences between the groups. Few associations were found between clinical and executive impairment profiles. Cognitive stimulation interventions, focused on inhibitory control, should be proposed in combination with psychotherapy.