Lymph Node Metastases Detection Using Gd2O3@PCD as Novel Multifunctional Contrast Imaging Agent in Metabolic Magnetic Resonance Molecular Imaging.

Axillary lymph node detection is crucial to staging and prognosis of the lymph node metastatic spread in breast cancer. Currently, lymphoscintigraphy and blue dye, as the conventional methods to localize sentinel lymph nodes (SLNs), are invasive and can only be performed during surgery. This study has had a novel hybrid gadolinium oxide nanoparticle coating with Cyclodextrin-based polyester as a high-relaxivity T1 magnetic resonance molecular imaging (MRMI) contrast agent (CA). Twelve female BALB/c mice were randomly divided into three groups of four mice; each group was injected with 4T1 cells to obtain metastasis lymph nodes and diagnosed by using the 3D T1W (VIBE) MRI (Siemens 3T, Prisma). The synthesized Gd2O3@PCD nanoparticles with a suitable particle size range of 20-40 nm have had much higher longitudinal relaxivity (r 1) for Gd2O3@PCD and Gd-DOTA (Dotarem) with the values of 3.98 mM-1·s-1 ± 0.003 and 2.71 mM-1·s-1 ± 0.005, respectively. Identical MR images in coronal views were subsequently obtained to create time-intensity curves of the right axillary lymph nodes and to measure the contrast ratio (CR). The peak CR and qualitative assessment of axillary lymph nodes at five-time points were evaluated. After subcutaneous injection, the contrast ratio of axillary lymph node and tumor in mice exhibited CR peak of Gd2O3@PCD and Dotarem with the values of 2.21 ± 0.06 and 0.40 ± 0.004 for lymph node and 2.54 ± 0.04 and 1.21 ± 0.007 for the tumor, respectively. Furthermore, the lumbar-aortic lymph node is weakly visible in the original coronal image. In conclusion, the use of Gd2O3@PCD nanoparticles as novel MRMI CAs enables high resolution for the detection of lymph node metastasis in mice with the potential capability for breast cancer diagnostic imaging.

Dosimetry and Radioenhancement Comparison of Gold Nanoparticles in Kilovoltage and Megavoltage Radiotherapy using MAGAT Polymer Gel Dosimeter.

BACKGROUND: Numerous unique characteristics of the nanosized gold, including high atomic number, low toxicity, and high biocompatibility make it one of the most appropriate nanostructures to boost radiotherapy efficacy. Many in-vivo and in-vitro investigations have indicated that gold nanoparticles (AuNPs) can significantly increase tumor injuries in low kilovoltage radiotherapy. While deep-lying tumors require much higher energy levels with greater penetration power, and investigations carried out in megavoltage energy range show contradictory results. OBJECTIVE: In this study, we quantitatively assess and compare dose enhancement factors (DEFs) obtained through AuNPs under radiation of Cobalt-60 source (1.25MeV) versus Iridium-192 source (380 KeV) using MAGAT gel dosimeter. MATERIAL AND METHODS: MAGAT polymer gel in both pure and combined with 0.2 mM AuNPs was synthesized. In order to quantify the effect of energy on DEF, irradiation was carried out by Co-60 external radiotherapy and Ir-192 internal radiotherapy. Finally, readings of irradiated and non-irradiated gels were performed by MR imaging. RESULTS: The radiation-induced R2 (1/T2) changes of the gel tubes doped with AuNPs compared to control samples, upon irradiation of beams released by Ir-192 source showed a significant dose enhancement (15.31% ±0.30) relative to the Co-60 external radiotherapy (5.85% ±0.14). CONCLUSION: This preliminary study suggests the feasibility of using AuNPs in radiation therapy (RT), especially in low-energy sources of brachytherapy. In addition, MAGAT polymer gel, as a powerful dosimeter, could be used for 3D visualization of radiation dose distribution of AuNPs in radiotherapy.

Synthesis, characterization and antifungal activity of a novel formulated nanocomposite containing Indolicidin and Graphene oxide against disseminated candidiasis.

OBJECTIVE: Candidiasis is one of the most opportunistic fungal infections in immunocompromised patients. The emergence of multidrug-resistant Candida species necessitates the development of novel antifungal agents. Seeking to the discovery of natural antifungal agents, this study aimed to synthesize a novel formulated nanocomposite containing Indolicidin (IN), antimicrobial peptide, and Graphene oxide (GO), kind of nanomaterial, against Candida growth using in vitro and in vivo experiments for the first time. METHODS: The formulated nanocomposite (GO-IN) synthetized and was characterized using scanning electron microscopy, X-ray power diffraction, and fourier transform infrared method analysis. The in vitro antifungal activity of fluconazole (FLU), GO, IN, and GO-IN was determined against Candida albicans (C. albicans) compared to control groups, cell cytotoxicity assay on human intestinal epithelial cells (IEP) and hemolytic activities were performed. Moreover, in vivo experiments of nanocomposite were assessed in BALB/c mice. RESULTS: Our results showed that nanocomposite had the highest inhibitory effect against C. albicans (MIC 3.12µg/mL) compared with flu (MIC 4µg/mL), IN (MIC 12.5µg/mL), and GO (MIC 6.25µg/mL). Viability of human intestinal cell line at the MIC concentration (3.12µg/mL) of nanocomposite (GO-IN) was detected as 60% (P<0.05). The results of hemolytic activity showed that nanocomposite cause 2.73% of red blood cell membrane damage. For in vivo experiments, infected mice were successfully treated with GO-IN once a day within 7 days. GO-IN treated group eliminated the Candida infection in the spleen and liver of BALB/c mice (P=0.001) similar to fluconazole. There was no significant difference in histological manifestations between flu and GO-IN groups. CONCLUSION: This study suggests that synergistic combination of GO and IN provide a new option, representing a potential therapeutic efficiency against disseminated candidiasis in an animal model as well as might be used as adjunct therapy in the management of candidiasis. However, further investigation is needed to evaluate the efficacy of the nanocomposite.

Turn-on fluorescent chemosensor for determination of lutetium ion.

A turn-on fluorescent chemosensor is introduced for the detection of Lu(3+) ion using N-[3-methyl]-2-[pyridine-2-amido] phenyl] pyridine-2-carboxamide (L) molecule. Fluorescent emission intensity of L enhances after binding to Lu(3+) ions in ethanol-water solution (1:9, v/v). The observed enhancement is the result of a strong covalent binding between Lu(3+) ion and L (the binding constant value is 2.0×10(6) mol(-1) L). The proposed optical chemosensor can be applied for the analysis of Lu(3+) ion in a linear range of 3.3×10(-7) to 1.0×10(-5) mol L(-1). The limit of detection was obtained 8.6×10(-7) mol L(-1). The probe exhibits high selectivity toward Lu(3+) ion in comparison with common metal ions. The proposed fluorescent chemosensor was successfully used in the determination of Lu(3+) ion in some water samples.

DNA methylation detection by a novel fluorimetric nanobiosensor for early cancer diagnosis.

A very sensitive and convenient fluorescence nanobiosensor for rapid detection of DNA methylation based on Fe3O4/Au core/shell nanoparticles has been developed. Specific site of CpG islands of adenomatous polyposis coli (APC), a well studied tumor suppressor gene, was used as the detection target DNA sequence. The characteristics of nanoparticles were determined by scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), UV-visible spectroscopy and X-ray diffraction (XRD) spectroscopy. Fe@Au nanoparticles functionalized by bounding of single stranded DNA (ssDNA) probe through sulfhydryl group at the 5' phosphate end. Then unmethylated and methylated complementary target ssDNA were hybridized with the immobilized ssDNA probe. Dipyridamole, a pharmaceutical agent used for the first time as a fluorescence probe which significantly interacted with hybridized unmethylated and methylated DNA. Upon the addition of the target unmethylated and methylated ssDNA, the fluorescence intensity increased in linear range by concentration of unmethylated ssDNA from 1.6 × 10(-15) to 6.6 × 10(-13)M with detection limit of 1.2 × 10(-16)M and on the other hand, fluorescence intensity declined linearly with concentration of 3.2 × 10(-15)-8.0 × 10(-13)M methylated DNA and detection limit was 3.1 × 10(-16)M. We have also shown that nanobiosensor could distinguish ratio of methylation in series of partially methylated DNA targets with identical sequences. A density functional theory (DFT) calculation was also performed to investigate the interaction between Dipyridamole with unmethylated and methylated cytosine. Finally real sample analysis suggested that nanobiosensor could have practical application for methylation detection in human plasma sample.

Selective recognition of Pr3+ based on fluorescence enhancement sensor.

(E)-2-(1-(4-hydroxy-2-oxo-2H-chromen-3-yl)ethylidene)hydrazinecarbothioamide (L) has been used to detect trace amounts of praseodymium ion in acetonitrile-water solution (MeCN/H2O) by fluorescence spectroscopy. The fluorescent probe undergoes fluorescent emission intensity enhancement upon binding to Pr(3+) ions in MeCN/H2O (9/1:v/v) solution. The fluorescence enhancement of L is attributed to a 1:1 complex formation between L and Pr(3+), which has been utilized as the basis for selective detection of Pr(3+). The sensor can be applied to the quantification of praseodymium ion with a linear range of 1.6×10(-7) to 1.0×10(-5) M. The limit of detection was 8.3×10(-8) M. The sensor exhibits high selectivity toward praseodymium ions in comparison with common metal ions. The proposed fluorescent sensor was successfully used for determination of Pr(3+) in water samples.