New tumor-targeted nanosized delivery carrier for oligonucleotides: characteristics in vitro and in vivo

Tianyang Zhou1,2, Xin Jia1, Huixiang Li3, Jin Wang3, Hongling Zhang1,2, Youmei A1,2, Zhenzhong Zhang1,21School of Pharmaceutical Sciences, 2Nanotechnology Research Center for Drugs, 3Department of Pathology, Medical School of Zhengzhou University, Zhengzhou, People’s Republic of ChinaBackground: The purpose of this study was to investigate the in vitro and in vivo characteristics of a new tumor-targeted nanosized delivery carrier for antisense oligonucleotide (ASON).Methods: Polyethylenimine (PEI) was used to condense ASON to form nanosized complexes (PEI/ASON), which were then modified using asparagine-glycine-arginine (NGR) peptide to obtain a tumor-targeted nanosized delivery carrier (NGR/PEI/ASON). The conditions required to form PEI/ASON were investigated.Results: A linear correlation between the natural logarithm of the N/P ratio (PEI to ASON) and the zeta potential of the PEI/ASON complexes was found, ranging from 1.5 to 5.0. The pH of the solution strongly influenced the zeta potential of the PEI/ASON complexes. PEI/ASON and NGR/PEI/ASON were stable in RPMI-1640 culture medium in the presence of Dextran 70. Incorporation of ASON into PEI/ASON and NGR/PEI/ASON complexes prevented degradation of ASON by DNase I.Conclusion: Both ASON/PEI and NGR/PEI/ASON complexes enhanced the uptake of ASON by EC9706 cells in vitro. In vivo, NGR/PEI/ASON complexes had the ability to target tumor tissues effectively.Keywords: nanosized delivery system, squamous cell carcinoma, antisense oligonucleotid

Andrographolide Alleviates Acute Brain Injury in a Rat Model of Traumatic Brain Injury: Possible Involvement of Inflammatory Signaling

Neuroinflammation plays an important role in secondary injury after traumatic brain injury (TBI). Andrographolide (Andro), a diterpenoid lactone isolated from Andrographis paniculata, has been demonstrated to exhibit anti-inflammatory activity in neurodegenerative disorders. This study therefore aimed to investigate the potential neuroprotective effects of Andro after TBI and explore the underlying mechanisms. In our study, we used a weight-dropped model to induce TBI in Sprague–Dawley rats, the neurological deficits were assessed using modified neurological severity scores, Fluoro-Jade B (FJB) and terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining were employed to examine neuronal degeneration and apoptosis after TBI, immunofluorescence was designed to investigate microglial activation. Quantitative Real-time PCR and ELISA were conducted to detect the expression levels of pro-inflammatory cytokines, Western blot was used to examine the expression level of proteins of relative signaling pathway. Our results showed that after Andro administration, the neurological deficit was attenuated, and the cerebral edema and apoptosis in brain tissues were also decreased following TBI. Both microglial activation and the expression of pro-inflammatory cytokines were significantly inhibited by Andro after TBI. Moreover, Andro inhibited NF-κB p65 subunit translocation and decreased the expression levels of phosphorylated extracellular signal regulated kinase (ERK) and p38 MAPK after TBI. Altogether, this study suggests that Andro could improve neurobehavioral function by inhibiting NF-κB and MAPK signaling pathway in TBI, which might provide a new approach for treating brain injury

Production of Chromophoric Dissolved Organic Matter (CDOM) in Laboratory Cultures of Arctic Sea Ice Algae

Chromophoric dissolved organic matter (CDOM) is highly enriched in bottom sea ice in the Arctic during ice algal blooms, giving rise to multifaceted ecological implications in both the sea ice and the underlying seawater. We conducted laboratory culture incubations to assess the potential role of ice algae in the accumulation of CDOM in Arctic sea ice. Non-axenic monocultures of Attheya septentrionalis and Nitzschia frigida and a natural ice algal assemblage (NIAA) were grown at 4 °C in an f/2 medium under cool white fluorescent light. Culture samples were collected several days apart throughout the exponential, stationary, and senescent phases, and analyzed for CDOM absorbance, chlorophyll a, and bacterial cell abundance. The cultures displayed apparent specific growth rates of algal and bacterial cells comparable to those in the field. Accumulations of CDOM were observed in all cultures during the time-course incubations, with the senescent phase showing the largest accumulations and the highest production rates. The senescent-phase production rate for NIAA was ~40% higher than that for A. septentrionalis. The chlorophyll a-normalized CDOM production rates in the cultures are comparable to those reported for Arctic first-year sea ice. The absorption spectra of CDOM in the cultures exhibited characteristic short-ultraviolet shoulders similar to those previously identified in sea ice. This study demonstrates that ice algal-derived CDOM can account for the springtime accumulation of CDOM in Arctic sea ice