ACS Applied Bio Materials
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2021
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IF 0
Quanyi Liu,Sheng Zhao,Yihong Zhang,Xueying An,Quan Wang,Sirong Li,Anqi Lin,Yan Du,Hui Wei
Serious lung diseases and other health problems caused by tobacco consumption are becoming more and more prominent all over the world. Scavenging the excessive harmful free radicals in cigarette smoke is proven to be an effective method in reducing the above problems. Carbon-based nanozymes have been widely studied due to their ability of scavenging free radicals. Accordingly, the biochar derived from silkworm excrement was reported as a nanozyme with free radical scavenging ability. The biochar nanozyme calcination at 900 °C with better free radical scavenging abilities was loaded into commercial cigarette filters for the following free radical scavenging verification in tobacco smoke. Mouse model results reveal the lung tissue could be improved by the addition of biochar nanozyme. This work not only provides an effective approach to reduce the harm caused by tobacco but also provides potential applications to rationally realize low-cost, ease of production, and a wide variety of biochar sources.
研究领域:
环境科学
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材料科学
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健康科学
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DOI
PubMed
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Gege Zeng,Zepeng He,Haihong Yang,Zhan Gao,Xueer Ge,Lixin Liu,Zhijia Liu,Yongming Chen
Much of current clinical interest has focused on mRNA therapeutics for the treatment of lung-associated diseases, such as infections, genetic disorders, and cancers. However, the safe and efficient delivery of mRNA therapeutics to the lungs, especially to different pulmonary cell types, is still a formidable challenge. In this paper, we proposed a cationic lipid pair (CLP) strategy, which utilized the liver-targeted ionizable lipid and its derived quaternary ammonium lipid as the CLP to improve liver-to-lung tropism of four-component lipid nanoparticles (LNPs) for in vivo mRNA delivery. Interestingly, the structure–activity investigation identified that using liver-targeted ionizable lipids with higher mRNA delivery performance and their derived lipid counterparts is the optimal CLP design for improving lung-targeted mRNA delivery. The CLP strategy was also verified to be universal and suitable for clinically available ionizable lipids such as SM-102 and ALC-0315 to develop lung-targeted LNP delivery systems. Moreover, we demonstrated that CLP-based LNPs were safe and exhibited potent mRNA transfection in pulmonary endothelial and epithelial cells. As a result, we provided a powerful CLP strategy for shifting the mRNA delivery preference of LNPs from the liver to the lungs, exhibiting great potential for broadening the application scenario of mRNA-based therapy.
研究领域:
药学
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纳米技术
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分子生物学
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治疗学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2021
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IF 9.229
Lan Wu,Lin-Ping Wu,Jingya Wu,Jin Sun,Zhonggui He,Cristina Rodríguez-Rodríguez,Katayoun Saatchi,Lea Ann Dailey,Urs O. Häfeli,Dongmei Cun,Mingshi Yang
Pulmonary delivery of small interfering RNA (siRNA)-based drugs is promising in treating severe lung disorders characterized by the upregulated expression of disease-causing genes. Previous studies have shown that the sustained siRNA release in vitro can be achieved from polymeric matrix nanoparticles based on poly(lactide-co-glycolide) (PLGA) loaded with lipoplexes (LPXs) composed of cationic lipid and anionic siRNA (lipid–polymer hybrid nanoparticles, LPNs). Yet, the in vivo efficacy, potential for prolonging the pharmacological effect, disposition, and safety of LPNs after pulmonary administration have not been investigated. In this study, siRNA against enhanced green fluorescent protein (EGFP-siRNA) was either assembled with 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) to form LPX or co-entrapped with DOTAP in PLGA nanoparticles to form LPNs. The disposition and clearance of LPXs and LPNs in mouse lungs were studied after intratracheal administration by using single-photon emission computed tomography/computed tomography (SPECT/CT) and gamma counting. Fluorescence spectroscopy, Western blot, and confocal laser scanning microscopy were used to evaluate the silencing of the EGFP expression mediated by the LPXs and LPNs after intratracheal administration to transgenic mice expressing the EGFP gene. The in vivo biocompatibility of LPXs and LPNs was investigated by measuring the cytokine level, total cell counts in bronchoalveolar lavage fluid, and observing the lung tissue histology section. The results showed that the silencing of the EGFP expression mediated by LPNs after pulmonary administration was both prolonged and enhanced as compared to LPXs. This may be attributed to the sustained release characteristics of PLGA, and the prolonged retention in the lung tissue of the colloidally more stable LPNs in comparison to LPXs, as indicated by SPECT/CT. The presence of PLGA effectively alleviated the acute inflammatory effect of cationic lipids to the lungs. This study suggests that PLGA-based LPNs may present an effective formulation strategy to mediate sustained gene silencing effects in the lung via pulmonary administration.
研究领域:
药剂学
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纳米技术
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分子生物学
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肺科学
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产品关联
DOI
PubMed
高影响因子
MEDICAL SCIENCE MONITOR
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2018
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IF 1.894
Lingling Wang,Yan Yin,Gang Hou,Jian Kang,Qiuyue Wang
Background Cigarette smoking is a well-known risk factor in multiple chronic pulmonary diseases. This study aims to investigate the role of peroxisome proliferator-activated receptor (PPAR) γ in cigarette smoking-induced inflammation. Material/Methods Cigarette smoking extract (CSE) was employed to induce inflammation in bronchial epithelial cells (BECs). After CSE administration, several autophagy-related proteins (Beclin1, autophagy-related gene (ATG)5, ATG7, p62, and LC3) and PPARγ levels were examined by western blot. Subsequently, PPARγ agonists and antagonist were used to treat CSE-induced BECs, several inflammatory factors (interleukin (IL)-6, IL-8, inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2) and autophagy-related proteins were detected to measure the inflammatory and autophagy levels. Then LC3 knockdown was performed to verify the role of autophagy in CSE-induced inflammation. Finally, the AMP-activated protein kinase (AMPK) and its downstream S6 kinase (S6K) were detected in CSE-stimulated BECs. Results CSE administration caused insufficient autophagy and the decrease of PPARγ in BECs. The PPARγ agonists ameliorate the CSE-induced inflammation and promote the autophagy development, evidenced by the changes of inflammatory factors and autophagy-related proteins. Loss-of-function experiments demonstrated that the PPARg played an anti-inflammatory role in an autophagy-dependent manner. In addition, CSE administration inactivated the AMPK signaling, which was restored by PPARγ agonists. The effects of PPARγ agonists on inflammation and autophagy could be abolished by AMPK inhibitor. Conclusions We demonstrated that PPARγ played a protective role in CSE-induced inflammation and autophagy by activating AMPK signaling in BECs, which may provide investigation basis for clinical therapy of chronic pulmonary diseases.
研究领域:
肺部疾病
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分子生物学
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细胞信号传导
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炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）