In addition to the pSTAT pathway, PLG nanoparticles also altered the phosphorylation status of SMAD2 and SMAD3 following TGF-β treatment to explanted primary fibroblast cultures generated from skin biopsy specimens from healthy individuals and patients with SSc for over 25 hours, a time point at which the TGF-β pathway has been activated for effective driving of myofibroblast differentiation. The gene discussed is SMAD2; the disease is systemic sclerosis.