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.

Publisher: BioMed Central Country of Publication: England NLM ID: 101152208 Publication Model: Electronic Cited Medium: Internet ISSN: 1477-3155 (Electronic) Linking ISSN: 14773155 NLM ISO Abbreviation: J Nanobiotechnology Subsets: MEDLINE

Original Publication: London : BioMed Central, 2003-

Benzylisoquinolines/*chemistry ; Calixarenes/*chemistry ; Cerebral Hemorrhage/*pathology ; Drug Carriers/*chemistry ; Metals/*chemistry ; Nanostructures/*chemistry ; Neuroprotective Agents/*chemistry ; Phenols/*chemistry ; Tetrahydroisoquinolines/*chemistry; Animals ; Benzylisoquinolines/administration & dosage ; Benzylisoquinolines/pharmacology ; Blood-Brain Barrier/drug effects ; Blood-Brain Barrier/metabolism ; Cerebral Hemorrhage/drug therapy ; Disease Models, Animal ; Humans ; Interleukin-1beta/metabolism ; Ions/chemistry ; Male ; Matrix Metalloproteinase 9/metabolism ; Mice ; Mice, Inbred C57BL ; Neurons/cytology ; Neurons/drug effects ; Neurons/metabolism ; Neuroprotective Agents/administration & dosage ; Neuroprotective Agents/pharmacology ; Organophosphonates/chemistry ; Reactive Oxygen Species/metabolism ; Tetrahydroisoquinolines/administration & dosage ; Tetrahydroisoquinolines/pharmacology

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 Fe ²⁺ 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.

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81860629 the National Natural Science Foundation of China; AA17292001 Major Project of Guangxi Science and Technology Department; 2018KF003 the Open Funds of the Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation; CMEMR2018-B06 State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University)

Keywords: Apoptosis; Dauricine; Ferroptosis; Intracerebral hemorrhage; Phosphonated calix[4]arene derivative; Targeted delivery

0 (Benzylisoquinolines)
0 (Drug Carriers)
0 (Interleukin-1beta)
0 (Ions)
0 (Metals)
0 (Neuroprotective Agents)
0 (Organophosphonates)
0 (Phenols)
0 (Reactive Oxygen Species)
0 (Tetrahydroisoquinolines)
0 (calix(4)arene)
130036-26-9 (Calixarenes)
8QTO90G5W5 (dauricine)
EC 3.4.24.35 (Matrix Metalloproteinase 9)

Date Created: 20200421 Date Completed: 20201105 Latest Revision: 20201105

20240829

PMC7168846

10.1186/s12951-020-00616-3

32306970