A pH-Responsive System Based on Fluorescence Enhanced Gold Nanoparticles for Renal Targeting Drug Delivery and Fibrosis Therapy

Int J Nanomedicine. 2020 Aug 6:15:5613-5627. doi: 10.2147/IJN.S260069. eCollection 2020.

Abstract

Background: Stimuli-responsive gold nano-assemblies have attracted attention as drug delivery systems in the biomedical field. However, there are challenges achieving targeted delivery and controllable drug release for specific diseases.

Materials and methods: In this study, a glutathione (GSH)-modified fluorescent gold nanoparticle termed AuLA-GSH was prepared and a Co2+-induced self-assembly drug delivery platform termed AuLA-GSH-Co was constructed. Both the pH-responsive character and drug loading behavior of AuLA-GSH-Co were studied in vitro. Kidney-targeting capability was investigated in vitro and in vivo. Finally, the anti-fibrosis efficiency of AuLA-GSH-Co in a mouse model of unilateral ureteral obstruction (UUO) was explored.

Results: AuLA-GSH-Co was sensitive to pH changes and released Co2+ in acidic conditions, allowing it to have controllable drug release abilities. AuLA-GSH-Co was found to improve cellular uptake of Co2+ ions compared to CoCl2 in vitro. AuLA-GSH exhibited specific renal targeting and prolonged renal retention time with low non-specific accumulation in vivo. Moreover, the anti-fibrosis efficiency of AuLA-GSH-Co was higher compared to CoCl2 in a mouse model of unilateral ureteral obstruction (UUO).

Conclusion: AuLA-GSH-Co could greatly enhance drug delivery efficiency with renal targeting capability and obviously relieve renal fibrosis, providing a promising strategy for renal fibrosis therapy.

Keywords: drug delivery; gold nanoparticles; pH sensitivity; renal fibrosis; self-assembly.

MeSH terms

  • Animals
  • Cell Line
  • Cobalt / chemistry
  • Cobalt / pharmacokinetics*
  • Disease Models, Animal
  • Drug Carriers / administration & dosage
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods*
  • Drug Liberation
  • Fibrosis
  • Fluorescence
  • Glutathione / chemistry
  • Gold / chemistry
  • Hydrogen-Ion Concentration
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology*
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / pathology
  • Metal Nanoparticles / administration & dosage
  • Metal Nanoparticles / chemistry*
  • Mice, Inbred BALB C
  • Mononuclear Phagocyte System / drug effects
  • Mononuclear Phagocyte System / metabolism
  • Rats
  • Ureteral Obstruction

Substances

  • Drug Carriers
  • Cobalt
  • Gold
  • Glutathione

Grants and funding

This work was supported by the Key project of Guangdong Natural Science Foundation (2018B0303110002), Shenzhen Sanming Project (SZSM20161204) and Shenzhen Science, Technology Innovation Commission Project (GJHZ20180754917, ZDSYS201909020 92855097) and China postdoctoral science foundation general program (2018M643135). The authors have no other relevant affiliations or financial involvement with any organizations or entities with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.