Face-to-face Assembly Strategy of Au Nanocubes: Induced Generation of Broad Hotspot Regions for SERS-Fluorescence Dual-Signal Detection of Intracellular miRNAs.

While designing anisotropic noble metal nanoparticles (NPs) can enhance the signal intensity of Raman dyes, more sensitive surface-enhanced Raman scattering (SERS) probes can be designed by oriented self-assembly of noble metal nanomaterials into dimers or higher-order nanoclusters. In this study, we engineered a self-assembly strategy in living cells for real-time fluorescence and SERS dual-channel detection of intracellular microRNAs (miRNAs), using Mg2+-dependent 8-17E DNAzyme sequences as the driving motors, gold nanocubes (AuNCs) as the driver components, and three-branched double-stranded DNA as the linking tool. The assembly selects adenine in DNA as a reporter molecule, simplifying the labeling process of Raman reporter molecules and reducing the synthesis process. In addition, adenine is stably distributed between the faces of AuNCs and the wide hotspot region gives good reproducibility of the adenine SERS signal. In this strategy, the SERS channel was consistently stable and more sensitive compared to the fluorescence channel. Among them, the detection limit of the SERS channel was 2.1 pM and the coefficient of variation was 1.26% in the in vitro liquid phase and 1.49% in MCF-7 cells. The strategy successfully achieved accurate tracking and quantification of miRNA-21 in cancer cells, showing good reproducibility in complex samples as well as cells. The reported strategy provides ideas for exploring intracellular specific triggering of nanoparticles for precise control of self-assembly.

Dual-targeted and dual-sensitive self-assembled protein nanocarrier delivering hVEGI-192 for triple-negative breast cancer.

Breast cancer is a highly prevalent malignancy worldwide among women with an increasing incidence in recent years. Triple-negative breast cancer (TNBC), a specific type of breast cancer, occurs primarily in young women and exhibits large tumor size, high clinical stage, and extremely poor prognosis with a high rate of lymph node, liver, and lung metastases. TNBC is insensitive to endocrine therapy and trastuzumab treatment, and there is an urgent need for effective therapeutics and treatment guidelines. However, investigations into antiangiogenic agents for the treatment of TNBC are ongoing. In this study, we successfully engineered a self-assembled protein nanocarrier TfRBP9-hVEGI-192-ELP fusion protein (TVEFP) to deliver the therapeutic protein, human vascular endothelial growth inhibitor (hVEGI-192). This was found to be effective in inhibiting tumor angiogenesis in vivo. The protein nanocarrier effectively inhibited the progression of TNBC in vivo and showed the behavior of self-assembly, thermoresponsiveness, enzyme stimulation-responsiveness, tumor-targeting, biocompatibility, and biodegradability. Near-infrared imaging studies showed that fluorescent dye-stained TVEFP effectively aggregated at the tumor site. The TVEFP nanocarrier significantly expands the application of the therapeutic protein hVEGI-192 and improves the imaging and biotherapeutic effects in TNBC, chiefly based on anti-angiogenesis effects.

Ultrasound-guided fine-needle aspiration biopsy of thyroid nodules <10 mm in the maximum diameter: does size matter?

OBJECTIVE: Ultrasound-guided fine-needle aspiration biopsy (US-FNAB) is a safe and effective method of screening malignant thyroid nodules such as papillary thyroid carcinoma. However, not much data are available regarding the diagnostic efficacy of US-FNAB for papillary thyroid microcarcinoma (≤10 mm in diameter). We aim to compare the diagnostic efficacy of US-FNAB on thyroid nodules between two groups divided by a diameter of 10 mm by correlating the cytological results of US-FNAB with the histopathologic diagnoses in selected patients. PATIENTS AND METHODS: Eight hundred twenty-two thyroid nodules (Group A: diameter ≤10 mm, n=620; Group B: diameter >10 mm, n=202) from 797 patients treated between March 2014 and June 2017 were retrospectively evaluated. Only nodules with Thyroid Imaging Reporting and Data System (TIRADS) categories 4-6 were enrolled and sampled by US-FNAB, followed by surgical resection. RESULTS: According to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) diagnostic categories, 94 thyroid nodules were classified as I, III and IV, and were excluded from the analysis. The resultant 728 thyroid nodules from 721 patients were analyzed. The malignant tendency (TBSRTC V and VI) rates on US-FNAB were 88.2% and 84.6% (P=0.202) in Group A and Group B, respectively, and the malignant rates were 89.5% and 86.9% (P=0.330), respectively, on histopathology. There was a high concordance between cytology and histopathology diagnoses (kappa value =0.797), and no statistical difference in terms of US-FNAB accuracy was found between the two groups (P=0.533). CONCLUSION: For thyroid nodules of TIRADS category 4-6, the diagnostic efficacy of US-FNAB is similar for thyroid nodules either smaller or greater than 10 mm in their maximum diameter.