Curcumin-PLGA NPs coated with targeting biomimetic personalized stem cell membranes for osteoarthritis therapy

Traditional drug delivery systems for OA treatments face limitations due to rapid clearance within the joint and low biocompatibility. Moreover, the inflammation associated with OA exacerbates tissue damage and delays the regenerative capacity of therapeutics. To overcome these limitations, an OA-specific drug delivery system designated dCOL2-CM-Cur-PNPs is developed herein to target OA cartilage for anti-inflammatory and cartilage regeneration purposes. This system is constructed using cell membranes obtained from induced pluripotent stem cell -derived mesenchymal stem cells (iMSC-CMs), poly(D,l-lactide-co-glycolide) (PLGA) nanoparticles loaded with the well-known anti-inflammatory and cartilage-regenerating agent curcumin (Cur-PNPs), and damaged type II collagen (dCOL2)-targeting phospholipids. Coating the Cur-PNPs with iMSC-CMs enhances the sustained release of curcumin and improves its cellular uptake by OA-induced chondrocytes. The dCOL2-CM-Cur-PNPs restores the chondrogenic properties of the OA-induced chondrocytes, inhibit the pro-inflammatory function of M1 macrophages, and promote the anti-inflammatory function of M2 macrophages. The dCOL2-targeting phospholipids integrated on the surface of the iMSC-CMs facilitate specific binding to OA cartilage, as validated by in-vitro and in-vivo experiments. Additionally, the dCOL2-CM-Cur-PNPs alleviate OA progression in a DMM rat model. This drug delivery system based on iMSC-CMs modified with dCOL2-targeting phospholipids demonstrates significant potential as a next-generation platform for promoting cartilage regeneration through OA-specific therapy.