Extracellular Matrix-Inspired Dendrimer Nanogels Encapsulating Cyclophosphamide for Systemic Sclerosis Treatment

Cyclophosphamide has a certain therapeutic effect on treating systemic sclerosis (SSc), while difficulties exist in controlling severe systematic side effects and enhancing targeting capacity. Here, inspired from the natural extracellular matrix composition, we propose a cyclophosphamide-encapsulated nanogel based on dendritic polymers polyamidoamine (PAMAM) for SSc treatment. We combine bovine serum albumin and generation 5 (G5) PAMAM dendrimers with polyphenol modification to obtain nanogels featured with antioxidant and anti-inflammatory effects. The nanogels can possess excellent biocompatibility and prevent fibroblasts from oxidative stress damage and TGF-β-mediated activation. Furthermore, in the bleomycin-induced SSc mouse model, dendrimer nanogels encapsulating cyclophosphamide also exhibit the ability to attenuate fibrosis by modulating immunity, suppressing inflammation, and reducing collagen synthesis. These findings underscore the value of this dendritic polymer nanogel in the treatment of chronic SSc, indicating its broader potential for clinical applications.