Nanoparticle functionalization with genetically-engineered mesenchymal stem cell membrane for targeted drug delivery and enhanced cartilage protection

Articular cartilage encounters structural damage and tissue degeneration during osteoarthritis. It is of great significance to effectively deliver the therapeutic drug to the location of the cartilage lesion. Nanoparticle-based biomimetic systems provide an important solution for drug delivery, but they still lack the active targeting capability. Although some physical and chemical modifications could decrease non-specific interactions to some extent, a specific bio-interaction for active targeting is still required for many biomedical purposes. In this study, we proposed genetically-engineered mesenchymal stem cell membrane-derived nanoparticles with the active targeting capability. BMSCs were engineered for the high expression of CXCR4 to actively migrate to the injured locations, and cell membrane of the engineered BMSCs was isolated and camouflaged to fluorescent nanoparticles. The modified nanoparticles that loaded with the therapeutic drug were incubated with IL-1β-induced injured articular chondrocytes and cartilage. The results invisibly demonstrated that these engineered nanoparticles could increase both cellular uptake and penetration depth in the target cells and tissues under inflammatory microenvironments to protect the injured cartilage. Therefore, this genetically-modified nanoparticle functionalization strategy is expected to provide evidence for active targeting in the tissue injury treatment.