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具有内在生物活性的多功能聚(柠檬酸-姜黄素)用于快速治疗肺损伤和耐甲氧西林金黄色葡萄球菌感染

Intrinsically bioactive multifunctional Poly(citrate-curcumin) for rapid lung injury and MRSA infection therapy.

作者信息

Leng Tongtong, Zhang Long, Ma Junping, Qu Xiaoyan, Lei Bo

机构信息

Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an, 710054, China.

Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.

出版信息

Bioact Mater. 2024 Jul 17;41:158-173. doi: 10.1016/j.bioactmat.2024.07.002. eCollection 2024 Nov.


DOI:10.1016/j.bioactmat.2024.07.002
PMID:39131630
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11314446/
Abstract

Dysregulated inflammation after trauma or infection could result in the further disease and delayed tissue reconstruction. The conventional anti-inflammatory drug treatment suffers to the poor bioavailability and side effects. Herein, we developed an amphiphilic multifunctional poly (citrate-polyglycol-curcumin) (PCGC) nano oligomer with the robust anti-inflammatory activity for treating acute lung injury (ALI) and (MRSA) infected wound. PCGC demonstrated the sustained curcumin release, inherent photoluminescence, good cellular compatibility, hemocompatibility, robust antioxidant activity and enhanced cellular uptake. PCGC could efficiently scavenge nitrogen-based free radicals, oxygen-based free radicals, and intracellular oxygen species, enhance the endothelial cell migration and reduce the expression of pro-inflammatory factors through the signal pathway. Combined the anti-inflammation and antioxidant properties, PCGC can shortened the inflammatory process. In animal model of ALI, PCGC was able to reduce the pulmonary edema, bronchial cell infiltration, and lung inflammation, while exhibiting rapid metabolic behavior . The MRSA-infection wound model showed that PCGC significantly reduced the expression of pro-inflammatory factors, promoted the angiogenesis and accelerated the wound healing. The transcriptome sequencing and molecular mechanism studies further demonstrated that PCGC could inhibit multiple inflammatory related pathways including , 15RA, . This work demonstrates that PCGC is efficient in resolving inflammation and promotes the prospect of application in inflammatory diseases as the drug-loaded therapeutic system.

摘要

创伤或感染后炎症调节失调可能导致进一步的疾病和组织重建延迟。传统的抗炎药物治疗存在生物利用度差和副作用的问题。在此,我们开发了一种具有强大抗炎活性的两亲性多功能聚(柠檬酸-聚乙二醇-姜黄素)(PCGC)纳米低聚物,用于治疗急性肺损伤(ALI)和耐甲氧西林金黄色葡萄球菌(MRSA)感染的伤口。PCGC表现出姜黄素的持续释放、固有光致发光、良好的细胞相容性、血液相容性、强大的抗氧化活性和增强的细胞摄取。PCGC可以有效地清除氮自由基、氧自由基和细胞内活性氧,通过信号通路增强内皮细胞迁移并降低促炎因子的表达。结合抗炎和抗氧化特性,PCGC可以缩短炎症过程。在ALI动物模型中,PCGC能够减轻肺水肿、支气管细胞浸润和肺部炎症,同时表现出快速的代谢行为。MRSA感染伤口模型表明,PCGC显著降低促炎因子的表达,促进血管生成并加速伤口愈合。转录组测序和分子机制研究进一步证明,PCGC可以抑制包括、15RA、在内的多种炎症相关通路。这项工作表明,PCGC在解决炎症方面是有效的,并作为载药治疗系统促进了其在炎症性疾病中的应用前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/9df2b926768e/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/f274a80dfe5c/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/ed4ad13f64d7/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/0045ebe04e31/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/345d93d72545/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/2b196d9aa528/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/7309f86e813b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/6849d2b34a38/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/ae1fd9c80055/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/bf6188891327/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/9df2b926768e/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/f274a80dfe5c/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/ed4ad13f64d7/sc1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/0045ebe04e31/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/345d93d72545/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/2b196d9aa528/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/7309f86e813b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/6849d2b34a38/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/ae1fd9c80055/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/bf6188891327/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/06c3/11314446/9df2b926768e/gr8.jpg

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