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血小板细胞膜仿生纳米系统在烟曲霉菌性角膜炎中的抗炎作用
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Abstract:
目的：构建一种血小板细胞膜包覆聚乳酸–羟基乙酸聚合物(poly (lactic-co-glycolic acid), PLGA)的仿生纳米系统(PLTm@PLGA)，评估其在烟曲霉菌性角膜炎中的抗炎作用。方法：制备并表征PLTm@PLGA。通过CCK-8、溶血试验检测生物安全性。实时荧光定量聚合酶链反应(RT-qPCR)检测烟曲霉菌刺激RAW264.7细胞后炎症因子TNF-α、IL-1β的mRNA表达水平。建立烟曲霉菌性角膜炎小鼠模型，观察治疗效果并进行炎症评分。结果：PLTm@PLGA呈球形，表现为典型的“壳–核”结构，其粒径为234.3 ± 8.9 nm。PLGA、PLTm@PLGA无明显细胞毒性，血液相容性好。PLTm@PLGA显著抑制RAW264.7细胞中TNF-α、IL-1β mRNA表达。PLTm@PLGA处理组临床炎症评分显著下降。结论：PLTm@PLGA具有良好生物相容性，抑制促炎细胞因子表达，减轻了小鼠烟曲霉菌性角膜炎的炎症反应。
Objective: Poly (lactic acid-co-glycolic acid) (PLGA) was coated with platelet membranes to construct a biomimetic NanoSystem (PLTm@PLGA), which was evaluated its protective effect in Aspergillus fumigatus keratitis. Methods: PLTm@PLGA was prepared and characterized. The biosafety was investigated by CCK-8 and hemolysis tests. The mRNA expression levels of TNF-α and IL-1β were detected by Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) in RAW264.7 cells stimulating with Aspergillus fumigatus. Mice models of Aspergillus fumigatus keratitis were established to observe the therapeutic effect and score the inflammation. Results: PLTm@PLGA is spherical and has a typical “shell-core” structure, and its particle size was 234.3 ± 8.9 nm. PLGA and PLTm@PLGA showed no significant cytotoxicity and hemolysis. PLTm@PLGA significantly inhibited the mRNA expression of TNF-α and IL-1β in RAW264.7 cells. The clinical inflammation score was significantly decreased in PLTm@PLGA group. Conclusion: PLTm@PLGA has great biosafety, and plays an anti-inflammatory role in Aspergillus fumigatus keratitis in mice by inhibiting the expression of inflammatory cytokines.
| [1] | Brown, L., Leck, A.K., Gichangi, M., et al. (2021) The Global Incidence and Diagnosis of Fungal Keratitis. The Lancet Infectious Diseases, 21, e49-e57. https://doi.org/10.1016/S1473-3099(20)30448-5 |
| [2] | Qiu, S., Zhao, G.-Q., Lin, J., et al. (2015) Natamycin in the Treatment of Fungal Keratitis: A Systematic Review and Meta-Analysis. International Journal of Ophthalmology, 8, 597-602. |
| [3] | Ahmadikia, K., Aghaei Gharehbolagh, S., Fallah, B., et al. (2021) Distribution, Prevalence, and Causative Agents of Fungal Keratitis: A Systematic Review and Meta-Analysis (1990 to 2020). Frontiers in Cellular and Infection Microbiology, 11, Article ID: 698780. https://doi.org/10.3389/fcimb.2021.698780 |
| [4] | Khani, S., Seyedjavadi, S.S., Hosseini, H.M., et al. (2020) Effects of the Antifungal Peptide Skh-AMP1 Derived from Satureja Khuzistanica on Cell Membrane Permeability, ROS Production, and Cell Morphology of Conidia and Hyphae of Aspergillus fumigatus. Peptides, 123, Article ID: 170195. https://doi.org/10.1016/j.peptides.2019.170195 |
| [5] | Jin, H., Luo, R., Li, J., et al. (2022) Inhaled Platelet Vesicle-Decoyed Biomimetic Nanoparticles Attenuate Inflammatory Lung Injury. Frontiers in Pharmacology, 13, Article ID: 1050224. https://doi.org/10.3389/fphar.2022.1050224 |
| [6] | Jin, H., Li, J., Zhang, M., et al. (2021) Berberine-Loaded Biomimetic Nanoparticles Attenuate Inflammation of Experimental Allergic Asthma via Enhancing IL-12 Expression. Frontiers in Pharmacology, 12, Article ID: 724525. https://doi.org/10.3389/fphar.2021.724525 |
| [7] | Robert, R., Nail, S., Marot-Leblond, A., et al. (2000) Adherence of Platelets to Candida Species in Vivo. Infection and Immunity, 68, 570-576. https://doi.org/10.1128/IAI.68.2.570-576.2000 |
| [8] | Rambach, G., Blum, G., Latgé, J.-P., et al. (2015) Identification of Aspergillus fumigatus Surface Components That Mediate Interaction of Conidia and Hyphae with Human Platelets. The Journal of Infectious Diseases, 212, 1140-1149. https://doi.org/10.1093/infdis/jiv191 |
| [9] | Fitzgerald, J.R., Foster, T.J. and Cox, D. (2006) The Interaction of Bacterial Pathogens with Platelets. Nature Reviews. Microbiology, 4, 445-457. https://doi.org/10.1038/nrmicro1425 |
| [10] | Kim, J.-K., Uchiyama, S., Gong, H., et al. (2021) Engineered Biomimetic Platelet Membrane-Coated Nanoparticles Block Staphylococcus aureus Cytotoxicity and Protect against Lethal Systemic Infection. Engineering, 7, 1149-1156. https://doi.org/10.1016/j.eng.2020.09.013 |
| [11] | Danhier, F., Ansorena, E., Silva, J.M., et al. (2012) PLGA-Based Nanoparticles: An Overview of Biomedical Applications. Journal of Controlled Release, 161, 505-522. https://doi.org/10.1016/j.jconrel.2012.01.043 |
| [12] | Ding, D. and Zhu, Q. (2018) Recent Advances of PLGA Micro/Nanoparticles for the Delivery of Biomacromolecular Therapeutics. Materials Science and Engineering: C, 92, 1041-1060. https://doi.org/10.1016/j.msec.2017.12.036 |
| [13] | Katara, R., Sachdeva, S. and Majumdar, D.K. (2017) Enhancement of Ocular Efficacy of Aceclofenac Using Biodegradable PLGA Nanoparticles: Formulation and Characterization. Drug Delivery and Translational Research, 7, 632-641. https://doi.org/10.1007/s13346-017-0416-1 |
| [14] | Hu, C.-M.J., Fang, R.H., Wang, K.-C., et al. (2015) Nanoparticle Biointerfacing by Platelet Membrane Cloaking. Nature, 526, 118-121. https://doi.org/10.1038/nature15373 |
| [15] | Sharma, S., Parmar, A., Kori, S., et al. (2016) PLGA-Based Nanoparticles: A New Paradigm in Biomedical Applications. TrAC Trends in Analytical Chemistry, 80, 30-40. https://doi.org/10.1016/j.trac.2015.06.014 |
| [16] | Liu, X., Sui, J., Li, C., et al. (2023) The Preparation and Therapeutic Effects of β-Glucan-Specific Nanobodies and Nanobody-Natamycin Conjugates in Fungal Keratitis. Acta Biomaterialia, 169, 398-409. https://doi.org/10.1016/j.actbio.2023.08.019 |
| [17] | Wu, T.G., Wilhelmus, K.R. and Mitchell, B.M. (2003) Experimental Keratomycosis in a Mouse Model. Investigative Ophthalmology & Visual Science, 44, 210-216. https://doi.org/10.1167/iovs.02-0446 |
| [18] | Kredics, L., Narendran, V., Shobana, C.S., et al. (2015) Filamentous Fungal Infections of the Cornea: A Global Overview of Epidemiology and Drug Sensitivity. Mycoses, 58, 243-260. https://doi.org/10.1111/myc.12306 |
| [19] | Hu, C.-M.J., Zhang, L., Aryal, S., et al. (2011) Erythrocyte Membrane-Camouflaged Polymeric Nanoparticles as a Biomimetic Delivery Platform. Proceedings of the National Academy of Sciences of the United States of America, 108, 10980-10985. https://doi.org/10.1073/pnas.1106634108 |
| [20] | Jan, N., Madni, A., Khan, S., et al. (2022) Biomimetic Cell Membrane‐Coated Poly(Lactic-Co-Glycolic Acid) Nanoparticles for Biomedical Applications. Bioengineering & Translational Medicine, 8, e10441. https://doi.org/10.1002/btm2.10441 |
| [21] | Jin, H., Zhao, Y., Yao, Y., et al. (2023) Therapeutic Effects of Tea Polyphenol-Loaded Nanoparticles Coated with Platelet Membranes on LPS-Induced Lung Injury. Biomaterials Science, 11, 6223-6235. https://doi.org/10.1039/D3BM00802A |
| [22] | Bout, D., Joseph, M., Pontet, M., et al. (1986) Rat Resistance to Schistosomiasis: Platelet-Mediated Cytotoxicity Induced by C-Reactive Protein. Science, 231, 153-156. https://doi.org/10.1126/science.3079916 |
| [23] | Ockenhouse, C.F., Magowan, C. and Chulay, J.D. (1989) Activation of Monocytes and Platelets by Monoclonal Antibodies or Malaria-Infected Erythrocytes Binding to the CD36 Surface Receptor in Vitro. Journal of Clinical Investigation, 84, 468-475. https://doi.org/10.1172/JCI114188 |
| [24] | Cosgrove, L.J., Apice, A.J., Haddad, A., et al. (1987) CR3 Receptor on Platelets and Its Role in the Prostaglandin Metabolic Pathway. Immunology Cell Biology, 65, 453-460. https://doi.org/10.1038/icb.1987.54 |
| [25] | Yeaman, M.R. (2010) Platelets in Defense against Bacterial Pathogens. Cellular and Molecular Life Sciences, 67, 525-544. https://doi.org/10.1007/s00018-009-0210-4 |
| [26] | Viriyakosol, S., Fierer, J., Brown, G.D., et al. (2005) Innate Immunity to the Pathogenic Fungus Coccidioides posadasii Is Dependent on Toll-Like Receptor 2 and Dectin-1. Infection and Immunity, 73, 1553-1560. https://doi.org/10.1128/IAI.73.3.1553-1560.2005 |
| [27] | Zhan, L., Peng, X., Lin, J., et al. (2020) Honokiol Reduces Fungal Load, Toll-Like Receptor-2, and Inflammatory Cytokines in Aspergillus fumigatus Keratitis. Investigative Opthalmology & Visual Science, 61, 48. https://doi.org/10.1167/iovs.61.4.48 |
| [28] | Zhu, Y., Peng, X., Zhang, Y., et al. (2021) Baicalein Protects against Aspergillus fumigatus Keratitis by Reducing Fungal Load and Inhibiting TSLP-Induced Inflammatory Response. Investigative Opthalmology & Visual Science, 62, 26. https://doi.org/10.1167/iovs.62.6.26 |
| [29] | Luan, S., Peng, X., Lin, J., et al. (2022) Gallic Acid Ameliorates Aspergillus fumigatus Keratitis through Reducing Fungal Load and Suppressing the Inflammatory Response. Investigative Opthalmology & Visual Science, 63, 12. https://doi.org/10.1167/iovs.63.12.12 |
