Macrophage membrane-camouflaged proanthocyanidin nano-modulators inhibit histone lactylation and target therapy for testicular ischemia-reperfusion injury

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Testicular torsion-detorsion induces testicular ischemia–reperfusion injury (TIRI), which is associated with excessive reactive oxygen species (ROS) generation. Proanthocyanidin (PC), a potent organic antioxidant, can inhibit oxidative stress. However, its inherent limitations, including poor targeting, short circulation time, and low membrane permeability, hinder its therapeutic efficacy. To overcome these limitations, a macrophage membrane-coated chitosan/hyaluronic acid (MM-CH) is developed as a biocompatible nanocarrier for encapsulating PC. Retaining critical macrophage membrane proteins, this biomimetic nanotherapeutic (MM-PC-CH) prolongs circulation and enhances active targeting to the injured testis. MM-PC-CH was effectively internalized by Sertoli cells. The activities of SOD, CAT and MDA, as well as the levels of IL-6, TNF-α and IL-10, apoptosis by flow cytometry and TUNEL assay were evaluated. The results demonstrated significant antioxidant, anti-inflammatory and anti-apoptotic effects, as well as inhibition of lactate levels. In vivo evaluations confirm that injected MM-PC-CH specifically accumulates in the injured testis, providing robust testicular protection and effectively alleviating TIRI. This study presents a promising biomimetic nanotherapy for alleviating testicular torsion by enhancing the targeted delivery of proanthocyanidin, providing an innovative strategy for precise treatment of various reproductive diseases with clinical translational value.