Semiconducting Polymer Nanoparticles for Photoactivatable Cancer Immunotherapy and Imaging of Immunoactivation.

Immunotherapy that stimulates the body's own immune system to kill cancer cells has emerged as a promising cancer therapeutic method. However, some types of cancer exhibited a low response rate to immunotherapy, and the high risk of immune-related side effects has been aroused during immunotherapy, which greatly restrict its broad applications in cancer therapy. Phototherapy that uses external light to trigger the therapeutic process holds advantages including high selectivity and efficiency, and low side effects. Recently, it has been proven to be able to stimulate immune response in the tumor region by inducing immunogenic cell death (ICD), the process of which was termed photo-immunotherapy, dramatically improving therapeutic specificity over conventional immunotherapy in several aspects. Among numerous optical materials for photo-immunotherapy, semiconducting polymer nanoparticles (SPNs) have gained more and more attention owing to their excellent optical properties and good biocompatibility. In this review, we summarize recent developments of SPNs for immunotherapy and imaging of immunoactivation. Different therapeutic modalities triggered by SPNs including photo-immunotherapy and photo-immunometabolic therapy are first introduced. Then, applications of SPNs for real-time monitoring immunoactivation are discussed. Finally, the conclusion and future perspectives of this research field are given.

A Biodegradable Stent with Surface Functionalization of Combined-Therapy Drugs for Colorectal Cancer.

In-stent restenosis caused by tumor ingrowth is a major problem for patients undergoing stent placement because conventional stents often lack sustainable antitumor capabilities. The aim of this work is to develop a silk fibroin (SF)-based nanofibrous membrane that is loaded with combined-therapy drugs by using electrospinning technologies, which is further coated on a polydioxanone (PDO) stent and used for the treatment of colorectal cancer (CRC). In order to improve treatment effectiveness, a combination of therapeutic drugs, i.e., curcumin (CUR) and 5-fluorouracil (5-FU), is dissolved into SF solution and then eletrospun onto the surface of the PDO stent. The morphology, secondary structure, and in vitro drug release profiles of the membranes are characterized. The antitumor efficacy is assessed in vitro and in vivo using a human CRC cell line and normal cells, and tumor-bearing nude mice. In vitro and in vivo studies on the nanofibrous memembrane-coating demonstrate improved antitumor effects for the CUR/5-FU dual drug system which can be attributed to cell cycle arrest in the S phase in association with induced apoptosis in tumor cells by blocking signal transducer and activator of transcription3 (Stat3) and nuclear factor kappa beta (NF-kB) signaling pathways, suggesting potential in the treatment of CRC in the future.

Melatonin Improves Laying Performance by Enhancing Intestinal Amino Acids Transport in Hens.

The high concentration of melatonin (MEL) in the intestinal mucosa suggests that it has a special physiological function in intestine. In hens, previous studies have shown that MEL treatment promoted egg-laying performance. Considering the importance of amino acids (AA) for egg formation, we hypothesized that MEL may enhance the intestinal absorption of AA from the feed, thus promoting egg laying performance. In this study, we supplemented the hens with MEL for two consecutive weeks. The results showed that, compared with control group, feeding with 0.625 mg MEL/kg diets gave rise to higher egg laying rate (by 4.3%, P = 0.016), increased eggshell thickness (by 16.9%, P < 0.01) and albumen height (by 4.5%, P = 0.042). Meanwhile, feeding with 0.625 and 2.5 mg MEL/kg diets could significantly increase serum levels of aspartic acid, threonine, serine, glutamic acid, glycine, alanine, isoleucine, leucine, tyrosine, phenylalanine, lysine, histidine, arginine, and proline. Furthermore, a 0.625 mg MEL/kg diets could significantly increase the expression of PepT1 (by 3949.9%), B0AT (by 6045.9%), b0, +AT (by 603.5%), and EAAT3 (by 412.7%) in the jejunum. Additionally, in the cultured intestinal crypt "organoids," treatment with 0.5 µM MEL could significantly enhance the expression of PepT1, b0, +AT and EAAT3 mRNAs by 35.4%, 110.0%, and 160.1%, respectively. Detection of MEL concentration in serum and intestinal fluid suggested that lower dosage of MEL feeding was mainly acted on intestine locally, and further increased intestinal antioxidases (GPx-3, SOD-1 or PRDX-3) mRNA expression. Taken together, we demonstrated that MEL feeding in laying hens could locally promote the expression and function of AA transporter in small intestine by up-regulating antioxidases expression, and finally elevate laying performance.

Supercritical carbon dioxide-developed silk fibroin nanoplatform for smart colon cancer therapy.

PURPOSE: To deliver insoluble natural compounds into colon cancer cells in a controlled fashion. MATERIALS AND METHODS: Curcumin (CM)-silk fibroin (SF) nanoparticles (NPs) were prepared by solution-enhanced dispersion by supercritical CO2 (SEDS) (20 MPa pressure, 1:2 CM:SF ratio, 1% concentration), and their physicochemical properties, intracellular uptake efficiency, in vitro anticancer effect, toxicity, and mechanisms were evaluated and analyzed. RESULTS: CM-SF NPs (<100 nm) with controllable particle size were prepared by SEDS. CM-SF NPs had a time-dependent intracellular uptake ability, which led to an improved inhibition effect on colon cancer cells. Interestingly, the anticancer effect of CM-SF NPs was improved, while the side effect on normal human colon mucosal epithelial cells was reduced by a concentration of ~10 µg/mL. The anticancer mechanism involves cell-cycle arrest in the G0/G1 and G2/M phases in association with inducing apoptotic cells. CONCLUSION: The natural compound-loaded SF nanoplatform prepared by SEDS indicates promising colon cancer-therapy potential.

An implantable and controlled drug-release silk fibroin nanofibrous matrix to advance the treatment of solid tumour cancers.

The development of more effective cancer therapeutic strategies are still critically required. The maximization of the therapeutic effect in combination with avoiding the severe side effects on normal tissues when using chemotherapy drugs is still an urgent problem that requires improvements urgently. Here we provide implantable and controllable drug-release that utilises silk fibroin (SF) as a nanofibrous drug delivery system (DDS) for cancer treatment. A nanofibrous structure with controllable fibre diameter (<100 nm) was produced. The drug release rate of the SF DDS was controlled by applying a post-treatment process. In vitro anti-cancer (HCT116) results indicated that curcumin (CM)-SF nanofibrous matrix had a superior anti-cancer potential when the concentration was >5 µg/mL. The mechanism could be explained by the cell cycle being held in the S phase. The toxic effect on normal cells (NCM460) was minimized by using a treatment concentration range (5-20 µg/mL). Implantation of this DDS into the tumour site inhibited the growth of solid tumour; this offers an alternative approach for novel cancer therapy.

PAF receptor antagonist Ginkgolide B inhibits tumourigenesis and angiogenesis in colitis-associated cancer.

Platelet activating factor (PAF), a potent pro-inflammatory phospholipid, has been found to trigger tumor growth and angiogenesis through its G-protein coupled receptor (PAFR). This study was aimed to investigate the potential role of PAF in azoxymethane (AOM)/dextran sulfate sodium (DSS) induced colitis-associated cancer (CAC), using PAFR antagonist Ginkgolide B (GKB). We found GKB up-regulated serum level of PAF-AH activity. As assessed by disease activity index (DAI), histological injury scores, leukocytes infiltration, and expression of pro-inflammatory cytokines, GKB ameliorated colonic inflammation and decreased tumor number and load in mice. GKB also decreased expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in tumor. These results suggest that PAFR antagonist might be a potential therapeutic strategy for CAC.

[Rapid assessment of volatile components in Baicao oils by headspace single drop microextraction coupled with gas chromatography].

A simple, fast GC method based on headspace single drop microextraction (HS-SDME) was used for the determination of menthol and methyl salicylate in Baicao oils. A special sample pretreatment method was performed by adding 10 microL the oil its methanol solution into 5 mL water in a caped 10 mL sample vial, a 1.5 microL microdrop of N,N-dimethylformamide with benzyl alcohol as internal standard was formed on the pinpoint of microsyringe needle, exposing 5 min at extraction temperature of 40 degrees C. After extraction, 0.5 microL of extract was directely injected into GC for analysis. The determination was carried out on a capillary column (0.53 mm x 30 m) with PEG as the stationary phase with FID as the detector. A temperature programm was employed. The excellent separation and detection of the target components was accomplished. The average recoveries varied between 95.4% and 99.2%, and relative standard deviations were less than 1.9%. The calibration curves were linear in the range of 1.26-80.5 mg x L(-1) for menthol (r = 0.999 0) and 2.49-1.59 x 10(2) mg x L(-1) for methyl salicylate (r = 0.999 1), respectively. The proposed method is proved to be simple, fast, accurate and low cost without complicated sample pretreatment HS-SDME is expected to be widely applied for the analysis of volatile components in traditional Chinese medicines.