Strategically Designed Antifibrotic Gold Nanoparticles to Prevent Collagen Fibril Formation

Because uncontrolled accumulation of collagen fibrils has been implicated in a series of pathologies, inhibition of collagen fibril formation has become one of the necessary strategies to target such collagen-linked complications. The presence of hydroxyproline (<i>Hyp</i>) at the Y position in (Gly-X-Y)_<i>n</i> sequence pattern of collagen is known to facilitate crucial hydrophobic and hydration-linked interactions that promote collagen fibril formation. Here, to target such <i>Hyp</i>-mediated interactions, we have synthesized uniform, thermostable, and hemocompatible <i>Hyp</i> coated gold nanoparticles (AuNPs^HYP) and have examined their inhibition effect on the fibril formation of type I collagen. We found that collagen fibril formation is strongly suppressed in the presence of AuNPs^HYP and no such suppression effect was observed in the presence of free <i>Hyp</i> and control Gly-coated nanoparticles at similar concentrations. Both isothermal titration calorimetric studies and bioinformatics analysis reveal possible interaction between <i>Hyp</i> and (Gly-Pro-Hyp) stretches of collagen triple-helical model peptides. Further, gold nanoparticles coated with proline (AuNPs^PRO) and tryptophan (AuNPs^TRP) also suppressed collagen fibril formation, suggesting their ability to interfere with aromatic-proline as well as hydrophobic interactions between collagen molecules. The <i>Hyp</i> molecules, when surface functionalized, are predicted to interfere with the <i>Hyp</i>-mediated forces that drive collagen self-assembly, and such inhibition effect may help in targeting collagen linked pathologies