Glomerulonephritis is a key factor in leading to
end-stage renal disease. Mesangial cell proliferation and macrophage infiltration are two prominent features linked in a vicious circle mechanism for
glomerulonephritis progression. Herein, a novel biomimetic pH-sensitive nanomicelle (MM/HA-DXM) was constructed to synergize
hyaluronic acid (HA)-activated macrophage phenotypic remodeling and
dexamethasone (DXM)-mediated mesangial cell killing for precise treatment of
glomerulonephritis. Owing to the camouflaged coating with endogenous macrophage membrane (MM), MM/HA-DXM could escape from RES phagocytosis and then be recruited to inflammatory glomerulus by active homing effect. Afterwards, HA-DXM nanomicelles ruptured in response to the weakly acidic
glomerulonephritis microenvironment, to locally release HA and DXM. On the one hand, DXM can inhibit the abnormal proliferation of mesangial cells. On the other hand, HA transformed pro-inflammatory M1 macrophages into anti-inflammatory M2 phenotype to improve the glomerular inflammatory microenvironment. In
doxorubicin-induced
glomerulonephritis models, results revealed that MM/HA-DXM could specifically "homing" to inflammatory renal tissue with 4.33-fold improvement in targeting performance. In addition, in vivo pharmacodynamic results proved that
after treatment with MM/HA-DXM, the
proteinuria level decreased to 2.33 times, as compared with that of control group, demonstrating a superior
therapeutic effect on
glomerulonephritis via this collaborative two-pronged anti-inflammatory
therapy strategy.