An osteoarthritis treatment comprised of TGFa nanoparticles that penetrate cartilage and persist in the joint.
Osteoarthritis (OA), a degenerative joint disease, is the most common form of arthritis, with
over 32 million adults affected in the US alone. Despite its prevalence and debilitating nature, no cure or disease-modifying treatment exists. The epidermal growth factor receptor (EGFR) signaling pathway controls many key cellular functions, and mice lacking EGFR develop OA. Transforming growth factor alpha (TGFa) stimulates the EGFR pathway and reduces OA in mice. However, its short circulation lifespan drastically reduces efficacy.
An engineered nanoparticle delivery system increases penetration of TGFa into the cartilage, prolongs retention of TGFa in the knee joint, and blocks OA progression in an animal model.
TGFa molecules are affixed to nanoparticles by specific chemistry. To reduce surface charge and increase cartilage penetration, the resulting TGFa-nanoparticles (TGFa-NP) were further engineered with a copolymer. The resulting TGFa-NP bound specifically to bovine cartilage cells and penetrated bovine cartilage tissue in vitro. Injecting engineered TGFa-NPs into the mouse knee joint prevented cartilage degeneration and promoted cartilage integrity over the course of months in a model of injury-induced OA.
Surgical destabilization of the medial meniscus (DMM) was used to induce OA in mice. Sham denotes mice that did not receive DMM. TGFa-NP and controls PBS, free TGFa (TGFa-DBCO), and control nanoparticles (Ctrl-NP) were injected in to the knee every 3 weeks after DMM. (A) Immunostaining of p-EGFR (brown) reveals enhanced EGFR activity in TGFa-NP treated mice 1 month after surgery. (B) Safranin O and Fast Green staining reveal cartilage (red) and non-cartilage (blue) in the knee joints of treated mice 2 and 3-months post DMM. Low: low magnification; high: high magnification. (C) OA severity at 3 months post-DMM was quantified by Mankin score. Higher scores indicate more severe OA. (D) Average uncalcified cartilage thickness (Uncal. Th) of knee joints 3 months post-DMM. Reduced thickness indicates more severe OA.