Nanotechnology-mediated anti-inflammatory therapy is emerging as a novel strategy for the treatment of inflammation-induced injury. However, one of the main hurdles for these anti-inflammatory nano-drugs is their potential toxic side effects in vivo. Herein, we uncovered that polydopamine (PDA) nanoparticles with their structure and chemical properties similar to melanin, a natural bio-polymer, displayed a significant anti-inflammation therapeutic effect on acute inflammation-induced injury. PDA with enriched phenol groups functioned as a radical scavenger to eliminate reactive oxygen species (ROS) generated during inflammatory responses. As revealed by in vivo photoacoustic imaging with a H2O2-specific nanoprobe, PDA nanoparticles remarkably reduced intracellular ROS levels in murine macrophages challenged with either H2O2 or lipopolysaccharide (LPS). The anti-inflammatory capacity of PDA nanoparticles was further demonstrated in murine models of both acute peritonitis and acute lung injury (ALI), where diminished ROS generation, reduced proinflammatory cytokines, attenuated neutrophil infiltration, and alleviated lung tissue damage were observed in PDA-treated mice after a single dose of PDA treatment. Our work therefore presents the great promise of PDA nanoparticles as a biocompatible nano-drug for anti-inflammation therapy to treat acute inflammation-induced injury.
Single-walled carbon nanotubes (SWNTs) with various unique properties have attracted great attention in cancer theranostics. Herein, SWNTs are coated with a shell of polydopamine (PDA), which is further modified by polyethylene glycol (PEG). The PDA shell in the obtained SWNT@PDA-PEG could chelate Mn2+, which together with metallic nanoparticulate impurities anchored on SWNTs offer enhanced both T1 and T2 contrasts under magnetic resonance (MR) imaging. Meanwhile, also utilizing the PDA shell, radionuclide 131I could be easily labeled onto SWNT@PDA-PEG, enabling nuclear imaging and radioisotope cancer therapy. As revealed by MR & gamma imaging, efficient tumor accumulation of SWNT@PDA-131I-PEG is observed after systemic administration into mice. By further utilizing the strong near-infarared (NIR) absorbance of SWNTs, NIR-triggered photothermal therapy in combination with 131I-based radioisotope therapy is realized in our animal experiments, in which a remarkable synergistic antitumor therapeutic effect is observed compared to monotherapies. Our work not only presents a new type of theranostic nanoplatform based on SWNTs, but also suggests the promise of PDA coating as a general approach to modify nano-agents and endow them with highly integrated functionalities.
Background: Hyperlactatemia upon admission is a documented risk factor for mortality in critically ill adult patients. However, the predictive significance of a single lactate measurement at admission for mortality in the general population of critically ill children remains uncertain. This study evaluated the predictive value of blood lactate levels at admission and determined the cut-off values for predicting in-hospital mortality in the critically ill pediatric population. Methods: We enrolled 1109 critically ill children who were admitted to a pediatric intensive care unit between July 2008 and December 2010. Arterial blood samples were collected in the first 2 hours after admission, and the lactate levels were determined. The Pediatric Risk of Mortality III (PRISM III) scores were calculated during the first 24 hours after admission. Results: Of the 1109 children admitted, 115 (10.4%) died in the hospital. The median (interquartile range) blood lactate level in critically ill children was 3.2 mmol/l (2.2-4.8). Among the children, 859 (77.5%) had a lactate concentration >2.0 mmol/l. The blood lactate level upon admission was significantly associated with mortality (odds ratio [OR] = 1.38; 95% confidence interval [CI], 1.30-1.46; p <0.001), even after adjustment for age, gender, and illness severity assessed by PRISM III (OR = 1.27; p <0.001). Multivariate regression analysis showed that a high blood lactate level (OR = 1.17; 95% CI, 1.07-1.29; p = 0.001), a high PRISM III score (OR = 1.15; 95% CI, 1.11-1.20; p <0.001), and a low serum albumin (OR =0.92; 95% CI, 0.88-0.96; p <0.001) were independent risk factors for mortality in critically ill children. Blood lactate achieved an area under-the-receiver-operating-characteristic curve (AUC) of 0.79 (p <0.001) for predicting mortality that was similar to that of PRISM III (AUC = 0.82; p <0.001). The p-value for a comparison of both AUCs was 0.318. Blood lactate displayed a sensitivity of 61% and a specificity of 86% in predicting mortality at the optimal cut-off value of 5.55 mmol/l, and the positive and negative likelihood ratios were 4.5 and 0.45, respectively. Conclusions: A high blood lactate level at admission is independently associated with and predictive of in-hospital mortality in the general population of critically ill children.
Differentiation of the acute myeloid leukemia (AML) cell line HL-60 can be induced by all trans-retinoic acid (ATRA); however, the mechanism regulating this process has not been fully characterized.