Metal ion-responsive nanocarrier derived from phosphonated calix[4]arenes for delivering dauricine specifically to sites of brain injury in a mouse model of intracerebral hemorrhage
Abstract Primary intracerebral hemorrhage (ICH) is a leading cause of long-term disability and death worldwide. Drug delivery vehicles to treat ICH are less than satisfactory because of their short circulation lives, lack of specific targeting to the hemorrhagic site, and poor control of drug releas...
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| Format: | Article |
| Language: | English |
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BMC
2020-04-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12951-020-00616-3 |
| _version_ | 1818013560359354368 |
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| author | Mingxin Li Guohao Liu Kaixuan Wang Lingfeng Wang Xiang Fu Lee Yong Lim Wei Chen Jingxin Mo |
| author_facet | Mingxin Li Guohao Liu Kaixuan Wang Lingfeng Wang Xiang Fu Lee Yong Lim Wei Chen Jingxin Mo |
| author_sort | Mingxin Li |
| collection | DOAJ |
| description | Abstract Primary intracerebral hemorrhage (ICH) is a leading cause of long-term disability and death worldwide. Drug delivery vehicles to treat ICH are less than satisfactory because of their short circulation lives, lack of specific targeting to the hemorrhagic site, and poor control of drug release. To exploit the fact that metal ions such as Fe2+ are more abundant in peri-hematomal tissue than in healthy tissue because of red blood cell lysis, we developed a metal ion-responsive nanocarrier based on a phosphonated calix[4]arene derivative in order to deliver the neuroprotective agent dauricine (DRC) specifically to sites of primary and secondary brain injury. The potential of the dauricine-loaded nanocarriers for ICH therapy was systematically evaluated in vitro and in mouse models of autologous whole blood double infusion. The nanocarriers significantly reduced brain water content, restored blood-brain barrier integrity and attenuated neurological deficits by inhibiting the activation of glial cells, infiltration by neutrophils as well as production of pro-inflammatory factors (IL-1β, IL-6, TNF-α) and matrix-metalloprotease-9. These results suggest that our dauricine-loaded nanocarriers can improve neurological outcomes in an animal model of ICH by reducing inflammatory injury and inhibiting apoptosis and ferroptosis. |
| first_indexed | 2024-04-14T06:34:43Z |
| format | Article |
| id | doaj.art-addc4959ac20454895881bb804e4ed56 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-14T06:34:43Z |
| publishDate | 2020-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-addc4959ac20454895881bb804e4ed562022-12-22T02:07:30ZengBMCJournal of Nanobiotechnology1477-31552020-04-0118111910.1186/s12951-020-00616-3Metal ion-responsive nanocarrier derived from phosphonated calix[4]arenes for delivering dauricine specifically to sites of brain injury in a mouse model of intracerebral hemorrhageMingxin Li0Guohao Liu1Kaixuan Wang2Lingfeng Wang3Xiang Fu4Lee Yong Lim5Wei Chen6Jingxin Mo7Clinical Research Center for Neurological Diseases of Guangxi Province, The Affiliated Hospital of Guilin Medical UniversityClinical Research Center for Neurological Diseases of Guangxi Province, The Affiliated Hospital of Guilin Medical UniversityClinical Research Center for Neurological Diseases of Guangxi Province, The Affiliated Hospital of Guilin Medical UniversityClinical Research Center for Neurological Diseases of Guangxi Province, The Affiliated Hospital of Guilin Medical UniversityDepartment of Pharmacy, The Affiliated Hospital of Guilin Medical UniversityDivision of Pharmacy, School of Allied Health, University of Western AustraliaClinical Research Center for Neurological Diseases of Guangxi Province, The Affiliated Hospital of Guilin Medical UniversityClinical Research Center for Neurological Diseases of Guangxi Province, The Affiliated Hospital of Guilin Medical UniversityAbstract Primary intracerebral hemorrhage (ICH) is a leading cause of long-term disability and death worldwide. Drug delivery vehicles to treat ICH are less than satisfactory because of their short circulation lives, lack of specific targeting to the hemorrhagic site, and poor control of drug release. To exploit the fact that metal ions such as Fe2+ are more abundant in peri-hematomal tissue than in healthy tissue because of red blood cell lysis, we developed a metal ion-responsive nanocarrier based on a phosphonated calix[4]arene derivative in order to deliver the neuroprotective agent dauricine (DRC) specifically to sites of primary and secondary brain injury. The potential of the dauricine-loaded nanocarriers for ICH therapy was systematically evaluated in vitro and in mouse models of autologous whole blood double infusion. The nanocarriers significantly reduced brain water content, restored blood-brain barrier integrity and attenuated neurological deficits by inhibiting the activation of glial cells, infiltration by neutrophils as well as production of pro-inflammatory factors (IL-1β, IL-6, TNF-α) and matrix-metalloprotease-9. These results suggest that our dauricine-loaded nanocarriers can improve neurological outcomes in an animal model of ICH by reducing inflammatory injury and inhibiting apoptosis and ferroptosis.http://link.springer.com/article/10.1186/s12951-020-00616-3Intracerebral hemorrhageDauricinePhosphonated calix[4]arene derivativeTargeted deliveryApoptosisFerroptosis |
| spellingShingle | Mingxin Li Guohao Liu Kaixuan Wang Lingfeng Wang Xiang Fu Lee Yong Lim Wei Chen Jingxin Mo Metal ion-responsive nanocarrier derived from phosphonated calix[4]arenes for delivering dauricine specifically to sites of brain injury in a mouse model of intracerebral hemorrhage Journal of Nanobiotechnology Intracerebral hemorrhage Dauricine Phosphonated calix[4]arene derivative Targeted delivery Apoptosis Ferroptosis |
| title | Metal ion-responsive nanocarrier derived from phosphonated calix[4]arenes for delivering dauricine specifically to sites of brain injury in a mouse model of intracerebral hemorrhage |
| title_full | Metal ion-responsive nanocarrier derived from phosphonated calix[4]arenes for delivering dauricine specifically to sites of brain injury in a mouse model of intracerebral hemorrhage |
| title_fullStr | Metal ion-responsive nanocarrier derived from phosphonated calix[4]arenes for delivering dauricine specifically to sites of brain injury in a mouse model of intracerebral hemorrhage |
| title_full_unstemmed | Metal ion-responsive nanocarrier derived from phosphonated calix[4]arenes for delivering dauricine specifically to sites of brain injury in a mouse model of intracerebral hemorrhage |
| title_short | Metal ion-responsive nanocarrier derived from phosphonated calix[4]arenes for delivering dauricine specifically to sites of brain injury in a mouse model of intracerebral hemorrhage |
| title_sort | metal ion responsive nanocarrier derived from phosphonated calix 4 arenes for delivering dauricine specifically to sites of brain injury in a mouse model of intracerebral hemorrhage |
| topic | Intracerebral hemorrhage Dauricine Phosphonated calix[4]arene derivative Targeted delivery Apoptosis Ferroptosis |
| url | http://link.springer.com/article/10.1186/s12951-020-00616-3 |
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