Biomimetic nanovesicles decorated with chemotactic and target membrane proteins for lupus nephritis treatment

Cell membrane-coated drug delivery systems show advantages of immune escape and bio-mimicking targeting capacity; attention in this area is focusing on further enhancing their targetability for specific cells to improve delivery efficacy and therapeutic effectiveness. Here, we report a novel biomimetic nano-delivery system featured with dual‑targeting and antioxidant capacity to combat refractory lupus nephritis (LN) and promote renal injury repair. The nanocarriers of the system were prepared by cloaking glucocorticoid methylprednisolone (MP)-loaded mesoporous dopamine nanoparticles (mPDA) with chemokine receptor 4 (CXCR4)-expressing mesenchymal stem cell membranes, which inherit chemotactic and immune escape properties. In addition, by inserting the bovine serum albumin (BSA) link onto the membrane surface, the mPDA-based biomimetic carriers (BMmPMs) demonstrate a neonatal Fc receptor (FcRn)-targeting capacity, contributing to specifical cellular delivery. Based on these features, we have demonstrated that the BMmPMs exhibited enhanced renal-specific distribution and targetability, effectively alleviating immune complex deposition-induced glomerular inflammation and damage without apparent systemic side effects in LN mouse models. Thus, we believe that the proposed functionalized cell membrane-coated nano-drug delivery system has promising implication for treating LN via dual-target immunomodulation.