Synergetic regulation of kupffer cells, extracellular matrix and hepatic stellate cells with versatile CXCR4-inhibiting nanocomplex for magnified therapy in liver fibrosis

Remodeling the hepatic fibrotic microenvironment with emerging nanotherapeutics: a comprehensive review

“…Anionic HA-containing NPs LSECs, Tregs Suppressing antigen-specific immune responses [29] AB diblock copolymers NPs LSECs, KCs Leading to immune inflammation [33] Stab2-containing NPs LSECs, Tregs Clearing of lipoproteins [30] Mannose-modified albumin NPs Macrophages TGFβ-siRNA to CD206 + as an anti-fibrotic strategy [37] CMC-containing NPs Macrophages Reducing host immune response [40] PS-containing NPs Macrophages Reducing collagen fiber deposition [42] silk or silicon-containing NPs Macrophages Pro-inflammatory phenotype [69] hydrogel particles M2-polarized macrophages Improving immunocompromised and impaired angiogenesis [108,109] DEX/HA-TK-ART PMs M2-polarized macrophages HIF-1α/NF-κB signaling cascade [90] mLNP-siHMGB1 Macrophages, HSCs Inhibiting the activation of HSCs [38] DSPE-PEG-CeO2 NPs Macrophages, HSCs Reducing inflammation [86] CNF HSCs, macrophages Increasing glycolysis and reprogramming and reducing initiated inflammatory [70] VA-SLNs HSCs Reducing PPARγ/SREBPs-mediated lipid accumulation [61] CS sulfate PMs HSCs Anti-fibrotic strategy [63] CS-coated green silver NPs HSCs Bounding to the fibrogenic protein TGF-β [65] hydrogels HSCs Blocking the TGF-β1/Smad pathway [66] RGD HSCs Inhibiting the proliferation of HSCs [82] Chol-PCX/miRNA NPs HSCs, T cells Disrupting the lipid metabolic network [73,74] GQD HSCs Inhibiting lipid peroxidation, apoptosis, and autophagy [87] CeO2 NPs HSCs Antioxidant effect [85] FPL HSCs Antioxidant effect [88] ChiBil carrying losartan HSCs attenuating iron death [89] PEG-PLGA-containing NPs LSECs, hepatocytes and HSCs Constricting abnormal blood vessels, reducing MVD [99] Self-assembled PMs LSECs, hepatocytes and HSCs Avoiding the hepatotoxicity and side effects [96] NPs laponite HUVECs enhancing HIF-1α and VEGF expression, accelerating neovascularization [110] and mannose receptors (MR) that produce inhibitory acquired immune responses. LSECs regulate adaptive immune responses directly by presenting antigens to T cells and also regulate natural killer T cells (NKT cells) by expressing CXCL16, and the cell surface ligand for CXCR6…”

“…aCD3/F/AN-induced lipid metabolic reprogramming specifically activates T cells [72]. A recent study synthesizes cholesterol-modified polymeric CXCR4 inhibitor (Chol-PCX) in the form of Chol-PCX/miRNA NPs and CXCL12/CXCR4 axis disrupts the lipid metabolic network of T cells for the amplified treatment of liver fibrosis [73,74], suggesting that nanotechnology-enabled T cell lipid metabolic reprogramming has the potential to be a new paradigm for immunometabolic therapy.…”

Balancing and Therapeutic Roles of CXCR4‐Inhibiting Nanomedicine via Synergetic Regulation of Hepatic Stellate Cells and Extracellular Matrix in Liver Injury†

“…PAMD and PAMD/Zn polymers were prepared according to the previous report, and their structure was demonstrated using 1H‐NMR (Figure S1). [ 15,24 ] Following hydrodynamic size and zeta potential measurements, PAMD/Zn exhibited stronger affinity…”

“…At a later pro‐inflammatory stage, AMD3100 administration will suppress the activation of HSCs due to CXCR4 overexpression on their surface, and thereby contributing to the blocking of pro‐fibrotic signals, leading to liver repair (Figure 1A). [ 15‐17 ]…”

“…The silencing of PAI‐1 with small interference RNA (siPAI‐1) can lead to degradation of ECM, thereby promoting liver repair. [ 15 ] Due to the strong interaction between HSCs and ECM in the fibrosis progression, the combination of CXCR4 inhibition and PAI‐1 silencing provides an attractive approach to treat liver injury. As a result, AMD3100‐based siRNA delivery systems may be effective in optimizing the therapeutic efficacy of liver diseases.…”