Hyaluronic acid-coated polymeric micelles with hydrogen peroxide scavenging to encapsulate statins for alleviating atherosclerosis
Abstract Inflammation and oxidative stress are two major factors that are involved in the pathogenesis of atherosclerosis. A smart drug delivery system that responds to the oxidative microenvironment of atherosclerotic plaques was constructed in the present study. Simvastatin (SIM)-loaded biodegrada...
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| Format: | Article |
| Language: | English |
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BMC
2020-12-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-020-00744-w |
| _version_ | 1818012082137726976 |
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| author | Dan Mu Jianhui Li Yu Qi Xuan Sun Yihai Liu Song Shen Yuyu Li Biao Xu Bing Zhang |
| author_facet | Dan Mu Jianhui Li Yu Qi Xuan Sun Yihai Liu Song Shen Yuyu Li Biao Xu Bing Zhang |
| author_sort | Dan Mu |
| collection | DOAJ |
| description | Abstract Inflammation and oxidative stress are two major factors that are involved in the pathogenesis of atherosclerosis. A smart drug delivery system that responds to the oxidative microenvironment of atherosclerotic plaques was constructed in the present study. Simvastatin (SIM)-loaded biodegradable polymeric micelles were constructed from hyaluronic acid (HA)-coated poly(ethylene glycol)-poly(tyrosine-ethyl oxalyl) (PEG-Ptyr-EO) for the purpose of simultaneously inhibiting macrophages and decreasing the level of reactive oxygen species (ROS) to treat atherosclerosis. HA coating endows the micelle system the ability of targeting CD44-positive inflammatory macrophages. Owing to the ROS-responsive nature of PEG-Ptyr-EO, the micelles can not only be degraded by enzymes, but also consumes ROS by itself at the pathologic sites, upon which the accumulation of pro-inflammatory macrophages is effectively suppressed and oxidative stress is alleviated. Consequently, the cellular uptake experiment demonstrated that SIM-loaded HA-coated micelles can be effectively internalized by LPS-induced RAW264.7 cells and showed high cytotoxicity against the cells, but low cytotoxicity against LO2 cells. In mouse models of atherosclerosis, intravenously SIM-loaded HA-coated micelles can effectively reduce plaque content of cholesterol, resulting in remarkable therapeutic effects. In conclusion, the SIM-loaded micelle system provides a promising and innovative option against atherosclerosis. |
| first_indexed | 2024-04-14T06:15:35Z |
| format | Article |
| id | doaj.art-14160859c4c64e3cb0c711bcef80f8f3 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-14T06:15:35Z |
| publishDate | 2020-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-14160859c4c64e3cb0c711bcef80f8f32022-12-22T02:08:12ZengBMCJournal of Nanobiotechnology1477-31552020-12-0118111210.1186/s12951-020-00744-wHyaluronic acid-coated polymeric micelles with hydrogen peroxide scavenging to encapsulate statins for alleviating atherosclerosisDan Mu0Jianhui Li1Yu Qi2Xuan Sun3Yihai Liu4Song Shen5Yuyu Li6Biao Xu7Bing Zhang8Department of Radiology, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolDepartment of Cardiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical UniversityDepartment of Cardiology, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolDepartment of Cardiology, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolDepartment of Cardiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical UniversityDepartment of Cardiology, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical UniversityDepartment of Cardiology, Nanjing Drum Tower Hospital, Medical School of Nanjing UniversityDepartment of Cardiology, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolDepartment of Radiology, Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolAbstract Inflammation and oxidative stress are two major factors that are involved in the pathogenesis of atherosclerosis. A smart drug delivery system that responds to the oxidative microenvironment of atherosclerotic plaques was constructed in the present study. Simvastatin (SIM)-loaded biodegradable polymeric micelles were constructed from hyaluronic acid (HA)-coated poly(ethylene glycol)-poly(tyrosine-ethyl oxalyl) (PEG-Ptyr-EO) for the purpose of simultaneously inhibiting macrophages and decreasing the level of reactive oxygen species (ROS) to treat atherosclerosis. HA coating endows the micelle system the ability of targeting CD44-positive inflammatory macrophages. Owing to the ROS-responsive nature of PEG-Ptyr-EO, the micelles can not only be degraded by enzymes, but also consumes ROS by itself at the pathologic sites, upon which the accumulation of pro-inflammatory macrophages is effectively suppressed and oxidative stress is alleviated. Consequently, the cellular uptake experiment demonstrated that SIM-loaded HA-coated micelles can be effectively internalized by LPS-induced RAW264.7 cells and showed high cytotoxicity against the cells, but low cytotoxicity against LO2 cells. In mouse models of atherosclerosis, intravenously SIM-loaded HA-coated micelles can effectively reduce plaque content of cholesterol, resulting in remarkable therapeutic effects. In conclusion, the SIM-loaded micelle system provides a promising and innovative option against atherosclerosis.https://doi.org/10.1186/s12951-020-00744-wSimvastatinROS-responsiveHyaluronic acidMacrophagesAntioxidative stress |
| spellingShingle | Dan Mu Jianhui Li Yu Qi Xuan Sun Yihai Liu Song Shen Yuyu Li Biao Xu Bing Zhang Hyaluronic acid-coated polymeric micelles with hydrogen peroxide scavenging to encapsulate statins for alleviating atherosclerosis Journal of Nanobiotechnology Simvastatin ROS-responsive Hyaluronic acid Macrophages Antioxidative stress |
| title | Hyaluronic acid-coated polymeric micelles with hydrogen peroxide scavenging to encapsulate statins for alleviating atherosclerosis |
| title_full | Hyaluronic acid-coated polymeric micelles with hydrogen peroxide scavenging to encapsulate statins for alleviating atherosclerosis |
| title_fullStr | Hyaluronic acid-coated polymeric micelles with hydrogen peroxide scavenging to encapsulate statins for alleviating atherosclerosis |
| title_full_unstemmed | Hyaluronic acid-coated polymeric micelles with hydrogen peroxide scavenging to encapsulate statins for alleviating atherosclerosis |
| title_short | Hyaluronic acid-coated polymeric micelles with hydrogen peroxide scavenging to encapsulate statins for alleviating atherosclerosis |
| title_sort | hyaluronic acid coated polymeric micelles with hydrogen peroxide scavenging to encapsulate statins for alleviating atherosclerosis |
| topic | Simvastatin ROS-responsive Hyaluronic acid Macrophages Antioxidative stress |
| url | https://doi.org/10.1186/s12951-020-00744-w |
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