CD147
‐Conjugated Minocycline Nanomicelles Alleviate Neuroinflammation and Improve Neurological Function Following Intracerebral Hemorrhage
Yang Liu, Yun Chen, Yuanyuan Liu, Zhe Li, Qingli Wang, V. Wee Yong, Ruixue Wei, Mengzhou Xue ABSTRACT
Background
Intracerebral hemorrhage (ICH) remains one of the most devastating subtypes of stroke, characterized by high mortality and limited therapeutic options. Neuroinflammation is recognized as a critical determinant of secondary brain injury following ICH. Minocycline, a broad‐spectrum tetracycline antibiotic, has been shown to attenuate hematoma expansion, reduce blood–brain barrier (BBB) disruption, and improve neurological outcomes in preclinical ICH models. However, its clinical translation has been limited by poor aqueous solubility, low bioavailability, and dose‐related systemic toxicity.
Methods
We designed a brain‐targeted nanotherapeutic system based on minocycline‐loaded polymeric nanomicelles conjugated with anti‐CD147 monoclonal antibodies (MINO@PNM@CD147). The nanomicelles were synthesized using a co‐solvent evaporation method, followed by covalent conjugation of CD147 antibodies via amide bond formation. The physicochemical properties, biocompatibility, and targeting efficiency of the formulation were characterized in vitro. Therapeutic efficacy was evaluated in a collagenase‐induced ICH mouse model using histopathological, biochemical, and behavioral assessments.
Results
MINO@PNM@CD147 exhibited a uniform spherical morphology with an average hydrodynamic diameter of 13.5 nm and high colloidal stability. In vitro studies demonstrated excellent cellular compatibility and effective suppression of pro‐inflammatory mediators in lipopolysaccharide (LPS)‐activated BV‐2 cells. In vivo fluorescence imaging confirmed targeted accumulation of MINO@PNM@CD147 in perihematomal regions. Treatment markedly reduced neuronal degeneration, microglia and astrocyte activation, leukocyte infiltration, and cell apoptosis, while significantly attenuating the release of inflammatory mediators. Moreover, MINO@PNM@CD147 administration led to substantial improvements in neurological function compared with free minocycline or non‐targeted formulations.
Conclusion
Our findings highlight that MINO@PNM@CD147 combines anti‐inflammatory efficacy with precise brain‐targeted delivery, thereby offering a potent and safe nanotherapeutic strategy for mitigating neuroinflammation and promoting recovery after ICH. This work provides a promising translational platform for nanomedicine‐based interventions in ICH.