Kidney Week

Abstract: SA-PO841

Self-Assembled Polypeptide Gold Nanoparticles Selectively Target the Kidney for High-Efficiency Anti-Fibrosis Treatment

Session Information

• Molecular Mechanisms of CKD - III
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 1903 CKD (Non-Dialysis): Mechanisms

Authors

• Tan, Lishan, Nanfang Hospital, Southern Medical University , Guangzhou, GUANGDONG, China

Lishan Tan,

• Lai, Xuandi, Department of Chemistry, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, Guangzhou, China

Xuandi Lai,

• Hu, Jianqiang, Department of Chemistry, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, Guangzhou, China

Jianqiang Hu,

• Li, Aiqing, Nanfang Hospital, Southern Medical University , Guangzhou, GUANGDONG, China

Aiqing Li,

Background

Many preclinical agents (e.g., cobalt chloride) have attracted great attentions because they can ameliorate chronic kidney fibrosis. However, many of these drugs are lack of kidney targeting ability or/and exhibit biological toxicity, which limits their clinical applications. Here we produced glutathione- and lipoic acid-modified Au nanoassemblies (GLAuNPs-Co) with good biocompatibility, high renal targeting capability and excellent anti-fibrosis efficacy through a Co²⁺-induced coordination self-assembled strategy.

Methods

The LAuNPs and GLAuNPs were investigated using transmission electron microscopy (TEM), dynamic light scattering (DLS), fourier transform infrared (FTIR) spectra and thermogravimetric analysis (TGA). In vitro, Cell Counting Kit-8 (CCK-8) and Elisa Kits were used to evaluate the biocompatibility of GLAuNPs. Celluar uptake mechanism was explored by fluorescence microscopy and inductively coupled plasma-mass spectrometry (ICP-MS). Organs’ distribution was examined using in- and ex-vivo fluorescence imaging software. The loading and release efficiency was evaluated by ICP-MS. The anti-fibrosis efficacy and mechanism were tested by pathological staining, western blot and real-time PCR in vivo using unilateral ureteral obstruction (UUO) mice.

Results

In aqueous solution, GLAuNPs-Co could self-assemble at neutral pH, and disassemble and release Co²⁺ when pH stwich to acid. Cytotoxicity and immunotoxicity assays and in vivo fluorescence imaging revealed that GLAuNPs had excellent biocompatibility, non-immunotoxicity and kidney-targeting ability. Pathological staining, western blot and real-time PCR analyses showed that GLAuNPs-Co had more excellent anti-fibrosis, anti-inflammatory, anti-oxidative stress, and anti-apoptosis efficacy than that of free CoCl₂ in UUO nephropathy mice.

Conclusion

With attractive characteristics of specific renal-targeting, controllable drug-release, non-toxicity and outstanding fibrosis therapeutic efficacy, the GLAuNPs-Co is hopeful to become a promising drug against renal fibrosis in clinic in the near future, which represents an innovative avenue of designing and developing therapy system for kidney diseases.