A sub-10-nm, folic acid-conjugated gold nanoparticle as self-therapeutic treatment of tubulointerstitial fibrosis

Abstract

Nanomedicines for treating chronic kidney disease (CKD) are on the horizon, yet their delivery to renal tubules where tubulointerstitial fibrosis occurs remains inefficient. We report a folic acid-conjugated gold nanoparticle that can transport into renal tubules and treat tubulointerstitial fibrosis in mice with unilateral ureteral obstruction. The 3-nm gold core allows for the dissection of bio–nano interactions in the fibrotic kidney, ensures the overall nanoparticle (~7 nm) to be small enough for glomerular filtration, and naturally inhibits the p38α mitogen-activated protein kinase in the absence of chemical or biological drugs. The folic acids support binding to selected tubule cells with overexpression of folate receptors and promote retention in the fibrotic kidney. Upon intravenous injection, this nanoparticle can selectively accumulate in the fibrotic kidney over the nonfibrotic contralateral kidney at ~3.6% of the injected dose. Delivery to the fibrotic kidney depends on nanoparticle size and disease stage. Notably, a single injection of this self-therapeutic nanoparticle reduces tissue degeneration, inhibits genes related to the extracellular matrix, and treats fibrosis more effectively than standard Captopril therapy. Our data underscore the importance of constructing CKD nanomedicines based on renal pathophysiology.

Targeting tumor suppressor p53 for organ fibrosis therapy

“…Ji et al developed a reduced glutathione-responsive NP-based drug delivery system to target activated cardiac fibroblasts, further in vivo study verified that the system improves the therapeutic efficacy of MI-induced cardiac fibrosis with lower systemic toxicity [ 126 ]. Another research demonstrated that 7 nm folic acid-conjugated gold nanoparticle can effectively inhibit renal fibrosis through targeting to renal tubule cells [ 127 ]. These results suggested that cell-type specific targeting therapy strategy may provide an effective treatment for organ fibrosis.…”

Nanotechnology in inflammation: cutting-edge advances in diagnostics, therapeutics and theranostics

“…Au NPs can also inhibit other inflammatory signaling pathways. For instance, Chan et al introduced a sub-10-nm Au NP (~7 nm) coated with PEG and folic acid (FA) for kidney fibrosis 238 . The outcomes demonstrated that the Au NP was more effective in reducing tissue degeneration and inhibiting the p38α enzyme compared to standard Captopril therapy 238 .…”

“…For instance, Chan et al introduced a sub-10-nm Au NP (~7 nm) coated with PEG and folic acid (FA) for kidney fibrosis 238 . The outcomes demonstrated that the Au NP was more effective in reducing tissue degeneration and inhibiting the p38α enzyme compared to standard Captopril therapy 238 . Shifting macrophage polarization from M1 to M2 plays key roles in resolving inflammation 239 .…”