A sub-10-nm, folic acid-conjugated gold nanoparticle as self-therapeutic treatment of tubulointerstitial fibrosis
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AbstractNanomedicines 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.
Acceptance Date14/09/2023
All Author(s) ListCecilia Ka Wing Chan, Cheuk Chun Szeto, Leo Kit Cheung Lee, Yu Xiao, Bohan Yin, Xiaofan Ding, Thomas Wai Yip Lee, James Yun Wong Lau, Chung Hang Jonathan Choi
Journal nameProceedings of the National Academy of Sciences USA
Year2023
Month10
Day9
Volume Number120
Issue Number42
PublisherNational Academy of Sciences
Article numbere2305662120
ISSN0027-8424
eISSN1091-6490
LanguagesEnglish-United States
Keywordsnanomedicine, gold nanoparticle, chronic kidney disease, fibrosis, renal tubules

Last updated on 2024-03-01 at 12:19