{"title":"包覆肿瘤细胞膜的普拉多肟纳米颗粒：对抗有机磷中毒对中枢神经系统影响的新策略。","authors":"Huaizhi Jiang, Yanli Liu, Chu Wang, Yunyang Song, Fanghui Wu, Yifeng Yin, Zhanjun Yang","doi":"10.2147/IJN.S516233","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>In this study, cell membrane-coated nanoparticles (CMCNPs) were loaded with the organophosphorus antidote Pralidoxime Chloride (PAM) to improve the ability of the drug to penetrate the blood‒brain barrier (BBB) and evade immune clearance, providing a novel drug delivery strategy for the treatment of central organophosphorus poisoning.</p><p><strong>Methods: </strong>1) The cell membranes of mouse melanoma cells (B16F10), breast cancer cells (4T1), glioblastoma cells (GL261), and monocytic macrophage leukemia cells (RAW264.7) were extracted, and their purities were verified. The cell membranes were combined with PAM in mesoporous silica (SiO<sub>2</sub>) spheres by ultrasonic fusion to prepare the CMCNPs. 2) The immune evasion ability of CMCNPs was evaluated by laser confocal microscopy and flow cytometry after coculture with macrophages. 3) HPLC was used to screen the best CMCNPs through an in vitro BBB model. 4) After the CMCNPs were injected into malathion-poisoned mice, the phosphate chloride concentration in the peripheral blood and brain homogenates was tested, and the rate of acetylcholinesterase (AChE) reactivation was determined.</p><p><strong>Results: </strong>All four types of CMCNPs were spherical particles with diameters of approximately 100 nm. Compared with unwrapped nanoparticles, CMCNPs exhibited a stronger immune evasion ability and enhanced BBB penetration ability in an in vitro BBB model. They also significantly prolonged the in vivo circulation time of PAM, increased its delivery dose to the central nervous system, and markedly increased cholinesterase activity in brain tissues. Furthermore, in an organophosphorus-poisoned mouse model, CMCNPs significantly improved the survival rate of intoxicated mice.</p><p><strong>Conclusion: </strong>In this study, CMCNPs with a significant BBB penetration ability and immune evasion ability were successfully prepared and improved the therapeutic effect of PAM on central organophosphate poisoning.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"8101-8118"},"PeriodicalIF":6.6000,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205708/pdf/","citationCount":"0","resultStr":"{\"title\":\"Nanoparticles Loaded with Pralidoxime Wrapped in Tumor Cell Membranes: A New Strategy to Counteract the Central Nervous System Effects of Organophosphate Poisoning.\",\"authors\":\"Huaizhi Jiang, Yanli Liu, Chu Wang, Yunyang Song, Fanghui Wu, Yifeng Yin, Zhanjun Yang\",\"doi\":\"10.2147/IJN.S516233\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>In this study, cell membrane-coated nanoparticles (CMCNPs) were loaded with the organophosphorus antidote Pralidoxime Chloride (PAM) to improve the ability of the drug to penetrate the blood‒brain barrier (BBB) and evade immune clearance, providing a novel drug delivery strategy for the treatment of central organophosphorus poisoning.</p><p><strong>Methods: </strong>1) The cell membranes of mouse melanoma cells (B16F10), breast cancer cells (4T1), glioblastoma cells (GL261), and monocytic macrophage leukemia cells (RAW264.7) were extracted, and their purities were verified. The cell membranes were combined with PAM in mesoporous silica (SiO<sub>2</sub>) spheres by ultrasonic fusion to prepare the CMCNPs. 2) The immune evasion ability of CMCNPs was evaluated by laser confocal microscopy and flow cytometry after coculture with macrophages. 3) HPLC was used to screen the best CMCNPs through an in vitro BBB model. 4) After the CMCNPs were injected into malathion-poisoned mice, the phosphate chloride concentration in the peripheral blood and brain homogenates was tested, and the rate of acetylcholinesterase (AChE) reactivation was determined.</p><p><strong>Results: </strong>All four types of CMCNPs were spherical particles with diameters of approximately 100 nm. Compared with unwrapped nanoparticles, CMCNPs exhibited a stronger immune evasion ability and enhanced BBB penetration ability in an in vitro BBB model. They also significantly prolonged the in vivo circulation time of PAM, increased its delivery dose to the central nervous system, and markedly increased cholinesterase activity in brain tissues. Furthermore, in an organophosphorus-poisoned mouse model, CMCNPs significantly improved the survival rate of intoxicated mice.</p><p><strong>Conclusion: </strong>In this study, CMCNPs with a significant BBB penetration ability and immune evasion ability were successfully prepared and improved the therapeutic effect of PAM on central organophosphate poisoning.</p>\",\"PeriodicalId\":14084,\"journal\":{\"name\":\"International Journal of Nanomedicine\",\"volume\":\"20 \",\"pages\":\"8101-8118\"},\"PeriodicalIF\":6.6000,\"publicationDate\":\"2025-06-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205708/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Nanomedicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/IJN.S516233\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"NANOSCIENCE & NANOTECHNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Nanomedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/IJN.S516233","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"NANOSCIENCE & NANOTECHNOLOGY","Score":null,"Total":0}
Nanoparticles Loaded with Pralidoxime Wrapped in Tumor Cell Membranes: A New Strategy to Counteract the Central Nervous System Effects of Organophosphate Poisoning.
Purpose: In this study, cell membrane-coated nanoparticles (CMCNPs) were loaded with the organophosphorus antidote Pralidoxime Chloride (PAM) to improve the ability of the drug to penetrate the blood‒brain barrier (BBB) and evade immune clearance, providing a novel drug delivery strategy for the treatment of central organophosphorus poisoning.
Methods: 1) The cell membranes of mouse melanoma cells (B16F10), breast cancer cells (4T1), glioblastoma cells (GL261), and monocytic macrophage leukemia cells (RAW264.7) were extracted, and their purities were verified. The cell membranes were combined with PAM in mesoporous silica (SiO2) spheres by ultrasonic fusion to prepare the CMCNPs. 2) The immune evasion ability of CMCNPs was evaluated by laser confocal microscopy and flow cytometry after coculture with macrophages. 3) HPLC was used to screen the best CMCNPs through an in vitro BBB model. 4) After the CMCNPs were injected into malathion-poisoned mice, the phosphate chloride concentration in the peripheral blood and brain homogenates was tested, and the rate of acetylcholinesterase (AChE) reactivation was determined.
Results: All four types of CMCNPs were spherical particles with diameters of approximately 100 nm. Compared with unwrapped nanoparticles, CMCNPs exhibited a stronger immune evasion ability and enhanced BBB penetration ability in an in vitro BBB model. They also significantly prolonged the in vivo circulation time of PAM, increased its delivery dose to the central nervous system, and markedly increased cholinesterase activity in brain tissues. Furthermore, in an organophosphorus-poisoned mouse model, CMCNPs significantly improved the survival rate of intoxicated mice.
Conclusion: In this study, CMCNPs with a significant BBB penetration ability and immune evasion ability were successfully prepared and improved the therapeutic effect of PAM on central organophosphate poisoning.
期刊介绍：
The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area.
With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field.
Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.
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