Cryptotanshinone-loaded biomimetic pH-sensitive liposomes for the treatment of liver fibrosis

Liver fibrosis is characterized by the aberrant accumulation of extracellular matrix (ECM) components, primarily due to the persistent activation of hepatic stellate cells (HSCs). It is well-known that chronic liver inflammation from various etiologies leads to hepatocellular damage, which activates HSCs, initiating and exacerbating fibrosis. This presents a significant challenge for therapeutic interventions aimed at restoring ECM balance. Here, we present CPT-pH@RLs, a novel drug delivery system consisting of pH-sensitive liposomes modified with erythrocyte membranes (RBCm), designed to deliver cryptotanshinone to the liver. The results of cellular uptake and real-time in vivo imaging indicate that the modification of RBCm reduces the uptake of CPT-pH@RLs by macrophages and prolongs the in vivo cycling time of these particles. CPT-pH@RLs effectively reduce liver inflammation by inhibiting secretion of interleukin-1β (IL-1β). Moreover, they improve liver function, decrease ECM deposition, and alleviate liver fibrosis. Our findings demonstrate that CPT-pH@RLs represent a safe and effective passive targeting drug delivery system for anti-inflammatory and ECM normalization therapies, offering a promising approach for the reversal of liver fibrosis.