Nanomaterial-based ophthalmic drug delivery.

The low bioavailability and side effects of conventional drugs for eye disease necessitate the development of efficient drug delivery systems. Accompanying the developments of nanofabrication techniques, nanomaterials have been recognized as promising tools to overcome these challenges due to their flexible and programmable properties. Given the advances achieved in material science, a broad spectrum of functional nanomaterials capable of overcoming various ocular anterior and posterior segment barriers have been explored to satisfy the demands for ocular drug delivery. In this review, we first highlight the unique functions of nanomaterials suitable for carrying and transporting ocular drugs. Then, various functionalization strategies are emphasized to endow nanomaterials with superior performance in enhanced ophthalmic drug delivery. The rational design of several affecting factors is essential for ideal nanomaterial candidates and is depicted as well. Lastly, we introduce the current applications of nanomaterial-based delivery systems in the therapy of different ocular anterior and posterior segment diseases. The limitations of these delivery systems as well as potential solutions are also discussed. This work will inspire innovative design thinking for the development of nanotechnology-mediated strategies for advanced drug delivery and treatment toward ocular diseases.

Conjugating Peptides onto 1D Rodlike Bionanoparticles for Enhanced Activity against Gram-Negative Bacteria.

Gram-negative bacteria, which possess an impermeable outer membrane, are responsible for many untreatable infections. The lack of development of new relevant antibiotics for over 50 years has increased threats. Peptides are regarded as the most promising alternatives to antibiotics. However, since the activities of existing peptides are not yet comparable to those of current antibiotics, there is an urgent need to improve their antibacterial efficiencies. Herein, we conjugate peptides onto one-dimensional rod-like tobacco mosaic virus (TMV). The peptides on the obtained nanoparticles (peptide-TMV) are hundreds of times superior to free peptides in combating Gram-negative bacteria. Through morphology and gene detection of Escherichia coli, it was revealed that following peptide-TMV application, the high osmotic pressure related to membrane damage and the generated reactive oxygen species cause Escherichia coli's death. In addition, peptide-TMV causes a downregulation of biofilm-related genes, inhibiting biofilm formation. This work paves the way to combat Gram-negative bacteria-related infection.

Membrane intercalation-enhanced photodynamic inactivation of bacteria by a metallacycle and TAT-decorated virus coat protein.

Antibiotic resistance has become one of the major threats to global health. Photodynamic inactivation (PDI) develops little antibiotic resistance; thus, it becomes a promising strategy in the control of bacterial infection. During a PDI process, light-induced reactive oxygen species (ROS) damage the membrane components, leading to the membrane rupture and bacteria death. Due to the short half-life and reaction radius of ROS, achieving the cell-membrane intercalation of photosensitizers is a key challenge for PDI of bacteria. In this work, a tetraphenylethylene-based discrete organoplatinum(II) metallacycle (1) acts as a photosensitizer with aggregation-induced emission. It self-assembles with a transacting activator of transduction (TAT) peptide-decorated virus coat protein (2) through electrostatic interactions. This assembly (3) exhibits both ROS generation and strong membrane-intercalating ability, resulting in significantly enhanced PDI efficiency against bacteria. By intercalating in the bacterial cell membrane or entering the bacteria, assembly 3 decreases the survival rate of gram-negative Escherichia coli to nearly zero and that of gram-positive Staphylococcus aureus to ∼30% upon light irradiation. This study has wide implications from the generation of multifunctional nanomaterials to the control of bacterial infection, especially for gram-negative bacteria.

Integration of Cell-Penetrating Peptides with Rod-like Bionanoparticles: Virus-Inspired Gene-Silencing Technology.

Inspired by the high gene transfer efficiency of viral vectors and to avoid side effects, we present here a 1D rod-like gene-silencing vector based on a plant virus. By decorating the transacting activator of transduction (TAT) peptide on the exterior surface, the TAT-modified tobacco mosaic virus (TMV) achieves a tunable isoelectric point (from ∼3.5 to ∼9.6) depending on the TAT dose. In addition to enhanced cell internalization, this plant virus-based vector (TMV-TAT) acquired endo/lysosomal escape capacity without inducing lysosomal damage, resulting in both high efficiency and low cytotoxicity. By loading silencer green fluorescent protein (GFP) siRNA onto the TMV-TAT vector (siRNA@TMV-TAT) and interfering with GFP-expressing mouse epidermal stem cells (ESCs/GFP) in vitro, the proportion of GFP-positive cells could be knocked down to levels even lower than 15% at a concentration of ∼100% cell viability. Moreover, by interfering with GFP-expressing highly metastatic hepatocellular carcinoma (MHCC97-H/GFP) tumors in vivo, treatment with siRNA@TMV-TAT complexes for 10 days achieved a GFP-negative rate as high as 80.8%. This work combines the high efficiency of viral vectors and the safety of nonviral vectors and may provide a promising strategy for gene-silencing technology.

[Study on the hemodynamic changes in solid thyroid nodules by ultrasound contrast quantitative analysis].

OBJECTIVE: To compare the difference between the different perfusional regions in solid thyroid nodules. METHODS: From October 2013 to May 2015, CEUS was performed in 59 patients who hospitalizated in Zhoushan Hospital with solid thyroid nodules before operation. The time-intensity curve (TIC) of normal thyroid tissue, tumor edge and tumor center was drawn to collect perfusion index like the peak intensity (PI), time to peak (TP), area under the curve (AUC), mean transit time (MTT). After surgery, immunohistochemical staining was performed to evaluate the MVD in surgical specimens.Quantitative parameters and MVD were assessed by the Spearman correlation analysis. RESULTS: There were 31 thyroid papillary carcinomas and 28 nodular goiters. In malignant tumor group, the PI of normal thyroid tissue, tumor edge and tumor center were 28% ± 6%, 21% ± 7% and 14% ± 5%, respectively, while the AUC and MVD of the same regions were (1 865 ± 1 079)%S, (1 376 ± 595)%S, (805 ± 412)%S and(33 ± 6), (27 ± 6)/HP, (17 ± 6)/HP, respectively. The differences were statistically significant. However, in benign tumor group, there was no obvious statistic difference in the quantitative parameters and MVD between the three regions. The PI values of thyroid carcinomas and nodular goiters all were positively correlated with MVD (r=0.819, r=0.838, P<0.05). CONCLUSIONS: The variance of perfusion parameters were valuable diagnostic basis in differential diagnosis between benign and malignant thyroid nodules. They were associated with MVD, which might reflect the microvessel distributional characteristics of neoplasm and might be one of bases used to evaluate neoplasm angiogenesis.

Nanoporous Carbon Nanofibers Decorated with Platinum Nanoparticles for Non-Enzymatic Electrochemical Sensing of H2O2.

We describe the preparation of nanoporous carbon nanofibers (CNFs) decorated with platinum nanoparticles (PtNPs) in this work by electrospining polyacrylonitrile (PAN) nanofibers and subsequent carbonization and binding of PtNPs. The fabricated nanoporous CNF-PtNP hybrids were further utilized to modify glass carbon electrodes and used for the non-enzymatic amperometric biosensor for the highly sensitive detection of hydrogen peroxide (H2O2). The morphologies of the fabricated nanoporous CNF-PtNP hybrids were observed by scanning electron microscopy, transmission electron microscopy, and their structure was further investigated with Brunauer-Emmett-Teller (BET) surface area analysis, X-ray photoelectron spectroscopy, X-ray diffraction, and Raman spectrum. The cyclic voltammetry experiments indicate that CNF-PtNP modified electrodes have high electrocatalytic activity toward H2O2 and the chronoamperometry measurements illustrate that the fabricated biosensor has a high sensitivity for detecting H2O2. We anticipate that the strategies utilized in this work will not only guide the further design and fabrication of functional nanofiber-based biomaterials and nanodevices, but also extend the potential applications in energy storage, cytology, and tissue engineering.