A Calixarene Assembly Strategy of Combined Anti-Neuroinflammation and Drug Delivery Functions for Traumatic Brain Injury Therapy
Excessive inflammatory reaction aggravates brain injury and hinders the recovery of neural function in nervous system diseases. Microglia, as the major players of neuroinflammation, control the progress of the disease. There is an urgent need for effective non-invasive therapy to treat neuroinflamma...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/27/9/2967 |
| _version_ | 1827672024986681344 |
|---|---|
| author | Chunxiao Wang Yu-Xuan Chang Xi Chen Lihuan Bai Heping Wang Yu-Chen Pan Chunqiu Zhang Dong-Sheng Guo Xue Xue |
| author_facet | Chunxiao Wang Yu-Xuan Chang Xi Chen Lihuan Bai Heping Wang Yu-Chen Pan Chunqiu Zhang Dong-Sheng Guo Xue Xue |
| author_sort | Chunxiao Wang |
| collection | DOAJ |
| description | Excessive inflammatory reaction aggravates brain injury and hinders the recovery of neural function in nervous system diseases. Microglia, as the major players of neuroinflammation, control the progress of the disease. There is an urgent need for effective non-invasive therapy to treat neuroinflammation mediated by microglia. However, the lack of specificity of anti-inflammatory agents and insufficient drug dose penetrating into the brain lesion area are the main problems. Here, we evaluated a series of calixarenes and found that among them the self-assembling architecture of amphiphilic sulfonatocalix[8]arene (SC8A12C) had the most potent ability to suppress neuroinflammation in vitro and in vivo. Moreover, SC8A12C assemblies were internalized into microglia through macropinocytosis. In addition, after applying the SC8A12C assemblies to the exposed brain tissue, we observed that SC8A12C assemblies penetrated into the brain parenchyma and eliminated the inflammatory factor storm, thereby restoring neurobiological functions in a mouse model of traumatic brain injury. |
| first_indexed | 2024-03-10T03:52:58Z |
| format | Article |
| id | doaj.art-b1ab914096b34bcc8505d18463ec7b55 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T03:52:58Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b1ab914096b34bcc8505d18463ec7b552023-11-23T08:52:16ZengMDPI AGMolecules1420-30492022-05-01279296710.3390/molecules27092967A Calixarene Assembly Strategy of Combined Anti-Neuroinflammation and Drug Delivery Functions for Traumatic Brain Injury TherapyChunxiao Wang0Yu-Xuan Chang1Xi Chen2Lihuan Bai3Heping Wang4Yu-Chen Pan5Chunqiu Zhang6Dong-Sheng Guo7Xue Xue8Laboratory of Theranostical Nanomedicine, State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, ChinaKey Laboratory of Functional Polymer Materials (Ministry of Education), State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, 94 Weijin Poad, Tianjin 300071, ChinaLaboratory of Theranostical Nanomedicine, State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, ChinaLaboratory of Theranostical Nanomedicine, State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, ChinaLaboratory of Theranostical Nanomedicine, State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, ChinaKey Laboratory of Functional Polymer Materials (Ministry of Education), State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, 94 Weijin Poad, Tianjin 300071, ChinaLaboratory of Theranostical Nanomedicine, State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, ChinaKey Laboratory of Functional Polymer Materials (Ministry of Education), State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, 94 Weijin Poad, Tianjin 300071, ChinaLaboratory of Theranostical Nanomedicine, State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, ChinaExcessive inflammatory reaction aggravates brain injury and hinders the recovery of neural function in nervous system diseases. Microglia, as the major players of neuroinflammation, control the progress of the disease. There is an urgent need for effective non-invasive therapy to treat neuroinflammation mediated by microglia. However, the lack of specificity of anti-inflammatory agents and insufficient drug dose penetrating into the brain lesion area are the main problems. Here, we evaluated a series of calixarenes and found that among them the self-assembling architecture of amphiphilic sulfonatocalix[8]arene (SC8A12C) had the most potent ability to suppress neuroinflammation in vitro and in vivo. Moreover, SC8A12C assemblies were internalized into microglia through macropinocytosis. In addition, after applying the SC8A12C assemblies to the exposed brain tissue, we observed that SC8A12C assemblies penetrated into the brain parenchyma and eliminated the inflammatory factor storm, thereby restoring neurobiological functions in a mouse model of traumatic brain injury.https://www.mdpi.com/1420-3049/27/9/2967calixarenesself-assemblyneuroinflammationmicrogliatraumatic brain injury |
| spellingShingle | Chunxiao Wang Yu-Xuan Chang Xi Chen Lihuan Bai Heping Wang Yu-Chen Pan Chunqiu Zhang Dong-Sheng Guo Xue Xue A Calixarene Assembly Strategy of Combined Anti-Neuroinflammation and Drug Delivery Functions for Traumatic Brain Injury Therapy Molecules calixarenes self-assembly neuroinflammation microglia traumatic brain injury |
| title | A Calixarene Assembly Strategy of Combined Anti-Neuroinflammation and Drug Delivery Functions for Traumatic Brain Injury Therapy |
| title_full | A Calixarene Assembly Strategy of Combined Anti-Neuroinflammation and Drug Delivery Functions for Traumatic Brain Injury Therapy |
| title_fullStr | A Calixarene Assembly Strategy of Combined Anti-Neuroinflammation and Drug Delivery Functions for Traumatic Brain Injury Therapy |
| title_full_unstemmed | A Calixarene Assembly Strategy of Combined Anti-Neuroinflammation and Drug Delivery Functions for Traumatic Brain Injury Therapy |
| title_short | A Calixarene Assembly Strategy of Combined Anti-Neuroinflammation and Drug Delivery Functions for Traumatic Brain Injury Therapy |
| title_sort | calixarene assembly strategy of combined anti neuroinflammation and drug delivery functions for traumatic brain injury therapy |
| topic | calixarenes self-assembly neuroinflammation microglia traumatic brain injury |
| url | https://www.mdpi.com/1420-3049/27/9/2967 |
| work_keys_str_mv | AT chunxiaowang acalixareneassemblystrategyofcombinedantineuroinflammationanddrugdeliveryfunctionsfortraumaticbraininjurytherapy AT yuxuanchang acalixareneassemblystrategyofcombinedantineuroinflammationanddrugdeliveryfunctionsfortraumaticbraininjurytherapy AT xichen acalixareneassemblystrategyofcombinedantineuroinflammationanddrugdeliveryfunctionsfortraumaticbraininjurytherapy AT lihuanbai acalixareneassemblystrategyofcombinedantineuroinflammationanddrugdeliveryfunctionsfortraumaticbraininjurytherapy AT hepingwang acalixareneassemblystrategyofcombinedantineuroinflammationanddrugdeliveryfunctionsfortraumaticbraininjurytherapy AT yuchenpan acalixareneassemblystrategyofcombinedantineuroinflammationanddrugdeliveryfunctionsfortraumaticbraininjurytherapy AT chunqiuzhang acalixareneassemblystrategyofcombinedantineuroinflammationanddrugdeliveryfunctionsfortraumaticbraininjurytherapy AT dongshengguo acalixareneassemblystrategyofcombinedantineuroinflammationanddrugdeliveryfunctionsfortraumaticbraininjurytherapy AT xuexue acalixareneassemblystrategyofcombinedantineuroinflammationanddrugdeliveryfunctionsfortraumaticbraininjurytherapy AT chunxiaowang calixareneassemblystrategyofcombinedantineuroinflammationanddrugdeliveryfunctionsfortraumaticbraininjurytherapy AT yuxuanchang calixareneassemblystrategyofcombinedantineuroinflammationanddrugdeliveryfunctionsfortraumaticbraininjurytherapy AT xichen calixareneassemblystrategyofcombinedantineuroinflammationanddrugdeliveryfunctionsfortraumaticbraininjurytherapy AT lihuanbai calixareneassemblystrategyofcombinedantineuroinflammationanddrugdeliveryfunctionsfortraumaticbraininjurytherapy AT hepingwang calixareneassemblystrategyofcombinedantineuroinflammationanddrugdeliveryfunctionsfortraumaticbraininjurytherapy AT yuchenpan calixareneassemblystrategyofcombinedantineuroinflammationanddrugdeliveryfunctionsfortraumaticbraininjurytherapy AT chunqiuzhang calixareneassemblystrategyofcombinedantineuroinflammationanddrugdeliveryfunctionsfortraumaticbraininjurytherapy AT dongshengguo calixareneassemblystrategyofcombinedantineuroinflammationanddrugdeliveryfunctionsfortraumaticbraininjurytherapy AT xuexue calixareneassemblystrategyofcombinedantineuroinflammationanddrugdeliveryfunctionsfortraumaticbraininjurytherapy |