AI Article Synopsis
- Hepatic stellate cell (HSC)-targeted delivery is a promising approach for treating liver fibrosis, but challenges include ineffective nanomaterial delivery and the complex environment of fibrotic livers.
- Researchers developed a multifunctional nanocomplex that combines CXCR4 inhibition, clodronate, and siRNA to enhance therapy by effectively targeting and regulating liver cells involved in fibrosis.
- This innovative nanocomplex improves drug delivery, enhances HSC uptake, and demonstrates expanded antifibrotic effects through the coordinated regulation of various liver cell types and extracellular components.
Article Abstract
Hepatic stellate cell (HSC)-targeted delivery is an attractive strategy for liver fibrosis therapy, but the efficacy is hampered by poor delivery of nanomaterials and complicated microenvironments of the fibrotic liver. Here, we report a versatile CXCR4-inhibiting nanocomplex composed of polymeric CXCR4 antagonism (PAMD, PA), CLD (clodronate) and siPAI-1 (siRNA of plasminogen activator inhibitor-1) that surmounts multiple barriers to improve the outcome by co-regulating Kupffer cells (KCs), extracellular matrix (ECM) and HSCs. Upon encountering biological barriers, the nanocomplex exerted penetrating and targeting functions, efficiently overcoming KCs capture, ECM trapping and nonspecific recognition of HSCs, finally contributing to the enhanced HSCs uptake. Moreover, an enlarged antifibrotic activity is realized through synergetic regulation of KCs apoptosis, ECM degradation and HSCs inactivation. Overall, such a versatile nanocomplex provides a framework for designing HSC-targeted delivery system and has valuable potential as a novel antifibrotic strategy.
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| http://dx.doi.org/10.1016/j.biomaterials.2022.121492 | DOI Listing |
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