Lipid-Based Nanocarriers for RNA Delivery.

RNA-interference (RNAi) agents such as small-interfering RNA (siRNA) and micro-RNA (miRNA) have strong potential as therapeutic agents for the treatment of a broad range of diseases such as malignancies, infections, autoimmune diseases and neurological diseases that are associated with undesirable gene expression. In recent years, several clinical trials of RNAi therapeutics especially siRNAs have been conducted with limited success so far. For systemic administration of these poorly permeable and easily degradable macromolecules, it is obvious that a safe and efficient delivery platform is highly desirable. Because of high biocompatibility, biodegradability and solid track record for clinical use, nanocarriers made of lipids and/or phospholipids have been commonly employed to facilitate RNA delivery. In this article, the key features of the major sub-classes of lipid-based nanocarriers, e.g. liposomes, lipid nanoparticles and lipid nanoemulsions, will be reviewed. Focus of the discussion is on the various challenges researchers face when developing lipid-based RNA nanocarriers, such as the toxicity of cationic lipids and issues related to PEGylated lipids, as well as the strategies employed in tackling these challenges. It is hoped that by understanding more about the pros and cons of these most frequently used RNA delivery systems, the pharmaceutical scientists, biomedical researchers and clinicians will be more successful in overcoming some of the obstacles that currently limit the clinical translation of RNAi therapy.

Ordering Ag nanowire arrays by a glass capillary: a portable, reusable and durable SERS substrate.

Assembly of nanowires into ordered macroscopic structures with new functionalities has been a recent focus. In this Letter, we report a new route for ordering hydrophilic Ag nanowires with high aspect ratio by flowing through a glass capillary. The present glass capillary with well-defined silver nanowire films inside can serve as a portable and reusable substrate for surface-enhanced Raman spectroscopy (SERS), which may provide a versatile and promising platform for detecting mixture pollutions. By controlling the flow parameters of nanowire suspensions, initially random Ag nanowires can be aligned to form nanowire arrays with tunable density, forming cambered nanowire films adhered onto the inner wall of the capillary. Compared with the planar ordered Ag nanowire films by the Langmuir-Blodgett (LB) technique, the cambered nanowire films show better SERS performance.

A general strategy for self-assembly of nanosized building blocks on liquid/liquid interfaces.

A family of water/oil interfaces is introduced to provide effective platforms for rapid fabrication of large-area self-assembled nanofilms composed of various nanosized building blocks, including nanoparticles (NPs), nanocubes (NC), nanowires (NWs), and nanosheets, at room temperature. As a general interfacial assembly method, NWs and NPs are co-assembled at the liquid/liquid interface. The as-prepared co-assembled Ag NW and Ag NC films show high surface-enhanced Raman spectroscopy (SERS) intensity, the SERS performance being strongly dependent on the number ratio of the two kinds of nanosized building blocks. The results demonstrate that this interfacial system provides a general method for the assembly of various nanosized building blocks with different shapes and dimensionalities, and thus paves an alternative pathway for further applications of macroscopic assemblies with different functionalities.

Three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the response and tolerance in hepatocellular carcinoma (HCC) patients treated by three-dimensional conformal radiotherapy (3DCRT) combined with. transcatheter arterial chemoembolization (TACE).</p><p><b>METHODS</b>Fourty-six HCC patients confirmed by cytology or histology were studied. All patients underwent TACE 1 to 3 courses. Then they received 3DCRT after an interval of about one month. 3DCRT was given with the field covering the tumor with a generous margin. 6 MV X-ray was used. The total dose was 30 - 54 Gy, in daily 2 Gy fractions. Immediate response was recorded according to the WHO criteria carried out by serial CT scan one month after 3DCRT. Irradiation toxicities were scored by the RTOG criteria. Acute liver toxicity was graded according to the common toxicity criteria (CTC) of National Cancer Institute. Late toxicity was focused on radiation-induced liver disease (RILD).</p><p><b>RESULTS</b>Partial response was observed in 8 (17.4%) patients. Stable disease and progressive disease was observed in 35 (76.1%) patients and 3 (6.5%) patients, respectively. No complete response was observed at the time of the response evaluation. The overall survival rate at 1-, 2- and 3-year was 60.9%, 39.1% and 28.3%, respectively, with a median survival period of 16 months. The 1-, 2- and 3-year local progression-free rate was 73.9%, 56.5% and 39.1%, respectively. The 1-, 2- and 3-year distant metastasis rate was 15.2%, 21.7% and 34.8%. Univariate analysis showed that favorable prognostic predictors for survival were: T3 stage, CACA 2001 stage I, absence of portal thrombosis, Child-Pugh grade A and irradiation dose of >45 Gy. Irradiation dose and liver cirrhosis were identified by Cox-regression analysis as independent predictors for survival. Two patients experienced CTC grade 1 acute hepatic toxicity and three patients experienced grade 3 acute hepatic toxicity. Two patients developed RILD. Three patients experienced RTOG grade 1 acute gastrointestinal complication and one patient experienced acute gastrointestinal bleeding. Five patients experienced RTOG grade 1 leucopenia, and five patients experienced grade 2 leucopenia.</p><p><b>CONCLUSION</b>3DCRT combined with TACE is safe and effective for HCC. It is worthy of a further dose escalation study.</p>