Metal-based mesoporous polydopamine with dual enzyme-like activity as biomimetic nanodrug for alleviating liver fibrosis

Abstract

Liver fibrosis is a common pathological stage in the development of several chronic liver diseases, and early intervention can effectively reverse the developing process. Excessive reactive oxygen species (ROS) can promote the activation of hepatic stellate cells (HSCs), but existing treatments have not addressed this problem. In this study, different metal-based mesoporous polydopamine (MPDA) was prepared by the soft template method, and their free radical scavenging abilities, as well as the efficacy and safety of the carriers were investigated, so as to select Cu²⁺-coordinated MPDA (CMP) as the optimal nanocarrier. CMP exhibited superior SOD- and CAT-like activities compared to MPDA. Subsequently, a novel liver-targeted nanodrug delivery system (Cur/CMPH) with biosafety was constructed. Moreover, Cur/CMPH consisted of CMP loaded with the antifibrotic drug curcumin (Cur/CMP) and coated hyaluronic acid (HA) with liver-targeting properties on the surface of Cur/CMP, thus effectively intervening in the progression of liver fibrosis. Cur/CMPH possessed uniform particle size, negative Zeta potential, excellent antioxidant capacity, and pH-responsive drug release. Furthermore, Cur/CMPH in vitro studies demonstrated efficient cellular uptake, inhibition of the proliferation of HSCs, and excellent intracellular ROS scavenging without cytotoxicity. Besides, Cur/CMPH had specific targeting effect on fibrotic liver as well as good accumulation ability. In vivo studies, Cur/CMPH showcased the combined therapeutic effect of Cur and CMP, which significantly decreased the deposition of collagen fibers and alleviated the degree of liver fibrosis with good biosafety. In summary, the construction of Cur/CMPH opens up a novel idea in the field of nanodrug delivery systems for the treatment of liver fibrosis.