Carbon dots with long-wavelength emissions, high quantum yield (QY) and good biocompatibility are highly desirable for biomedical applications. Herein, a green, facile hydrothermal synthesis of highly efficient red emissive nitrogen-doped carbonized polymer dots (CPDs) with optimal emission at around 630 nm are reported. The red emissive CPDs possess a variety of superior properties including excellent water dispersibility, good biocompatibility, narrow bandwidth emission, an excitation-independent emission, and high QY (10.83% (in water) and 31.54% (in ethanol)). Further studies prove that such strong red fluorescence is ascribed to the efficient conjugated aromatic π systems and hydrogen bonds of CPDs. And the fluorescence properties of CPDs can be regulated by adjusting the dosage of HNO before the reaction. Additionally, the as-prepared CPDs are successfully used as a fluorescent probe for bioimaging, both in vitro and in vivo. More importantly, biodistribution results demonstrate that most CPDs and their metabolites are not only excreted in urine but also excreted by hepatobiliary system in a rapid manner. Besides, the CPDs could easily cross the blood brain barrier, which may provide a valuable strategy for the theranostics of some brain diseases through real-time tracking.
The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.201906641. Development of high-performance carbon dots (CDs) with emission wavelength longer than 660 nm (deep red emission) is critical in deep-tissue bioimaging, yet it is still a major challenge to obtain CDs with both narrow full width at half maximum (FWHM) and high deep red/ near-infrared emission yield. Here, deep red emissive carbonized polymer dots (CPDs) with unprecedented FWHM of 20 nm are synthesized. The purified CPDs in dimethyl sulfoxide (DMSO) solution possess quantum yield (QY) as high as 59% under 413 nm excitation, as well as recorded QY of 31% under 660 nm excitation in the deep red fluorescent window. Detailed characterizations identify that CPDs have unique polymer characteristics, consisting of carbon cores and the shells of polymer chains, and π conjugated system formed with N heterocycles and aromatic rings governs the single photoluminescence (PL) center, which is responsible for high QY in deep red emissive CPDs with narrow FWHM. The CPDs exhibit strong absorption and emission in the deep red light region, low toxicity, and good biocompatibility, making them an efficient probe for both one-photon and two-photon bioimaging. CPDs are rapidly excreted via the kidney system and hepatobiliary system.
The biocompatibility of biomaterials is essentially for its application. The aim of current study was to evaluate the biocompatibility of poly(lactic-co-glycolic acid) (PLGA)/gelatin/nanohydroxyapatite (n-HA) (PGH) nanofibers systemically to provide further rationales for the application of the composite electrospun fibers as a favorable platform for bone tissue engineering. The PGH composite scaffold with diameter ranging from nano- to micrometers was fabricated by using electrospinning technique. Subsequently, we utilized confocal laser scanning microscopy (CLSM) and MTT assay to evaluate its cyto-compatibility in vitro. Besides, real-time quantitative polymerase chain reaction (qPCR) analysis and alizarin red staining (ARS) were performed to assess the osteoinductive activity. To further test in vivo, we implanted either PLGA or PGH composite scaffold in a rat subcutaneous model. The results demonstrated that PGH scaffold could better support osteoblasts adhesion, spreading, and proliferation and show better cyto-compatibility than pure PLGA scaffold. Besides, qPCR analysis and ARS showed that PGH composite scaffold exhibited higher osteoinductive activity owing to higher phenotypic expression of typical osteogenic genes and calcium deposition. The histology evaluation indicated that the incorporation of Gelatin/nanohydroxyapatite (GH) biomimetics could significantly reduce local inflammation. Our data indicated that PGH composite electrospun nanofibers possessed excellent cyto-compatibility, good osteogenic activity, as well as good performance of host tissue response, which could be versatile biocompatible scaffolds for bone tissue engineering.
BackgroundInterleukin (IL)-5 is believed to be a key cytokine in eosinophil inflammatory infiltration in asthma. Previous clinical trials have evaluated the efficacy and safety of mepolizumab, a monoclonal antibody against IL-5, in patients with asthma. However, most of these studies were small, the conclusions were inconsistent, and the precise effects are therefore debatable.MethodsA meta-analysis of randomized placebo-controlled trials was conducted to evaluate the effect of intravenous infusion of mepolizumab on clinical outcomes in patients with asthma. Trials were searched in PubMed, Embase, Web of Science, Cochrane CENTRAL, Scopus, reviews, and reference lists of relevant articles. The outcome variables analyzed included eosinophil counts in blood and sputum, airways outcome measures, exacerbations, asthma control, and quality of life scores.ResultsSeven studies met final inclusion criteria (total n = 1131). From the pooled analyses, mepolizumab significantly reduced eosinophils in blood (MD −0.29×109/L, 95% CI −0.44 to −0.14×109/L, P = 0.0001) and sputum (MD −6.05%, 95% CI −9.34 to −2.77%, P = 0.0003). Mepolizumab was also associated with significantly decreased exacerbation risk than placebo (OR 0.30, 95%CI 0.13 to 0.67, P = 0.004), and with a significant improvement in the scores on the Asthma Quality of Life Questionnaire (AQLQ) (MD 0.26, 95% CI 0.03 to 0.49, P = 0.03) in patients with eosinophilic asthma. There were no statistical differences between the groups with respect to FEV1, PEF, or histamine PC20 (all P>0.05), and a non-significant trend for improvement in scores on the Juniper Asthma Control Questionnaire (JACQ) (MD −0.21, 95% CI −0.43 to 0.01, P = 0.06) in the mepolizumab group was observed.ConclusionsMepolizumab reduces the risk of exacerbations and improves quality of life in patients with eosinophilic asthma, but no significant improvement in lung function outcomes was observed. Further research is required to establish the possible role of anti–IL-5 as a therapy for asthma.
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