Quantum dots as biocompatible small RNA nanocarriers modulating macrophage polarization to treat Asherman’s syndrome

Macrophages play a key role in host defense and inflammation, with polarization ranging from pro-inflammatory M1 to anti-inflammatory M2 states. However, effective modulation of macrophage polarity via nucleotide delivery is challenging. This study developed polyethyleneimine-modified carboxyl quantum dots (QDP) as a biocompatible carrier for small RNA delivery to modulate macrophage polarization. QDP-mediated delivery of miR-10a (QDP/miR-10a) rebalanced macrophage polarity and alleviated uterine inflammation and fibrosis in a mouse model of Asherman's syndrome (AS). In vitro, QDP effectively delivered small RNA into RAW 264.7 cells without cytotoxicity, converting LPS-induced M1 to M2 macrophages by inhibiting NF-κB, MAPK, and AKT signaling. In vivo, QDP/miR-10a reduced M1 macrophages, restored polarization, and enhanced uterine restoration in AS mice without affecting systemic immunity. Thus, QDP represents a safe and effective nanocarrier for small RNA delivery to modulate macrophage polarization for inflammatory disease treatment, including AS.