Chitosan Oligosaccharide-Functionalized Ruthenium-Curcumin Nanodots for Targeted Therapy of Acute Kidney Injury
Qin Yu1, Xue-Ying Tan2, Xian Liu1
1Department of Urology, Beilun People's Hospital, Ningbo, Zhejiang, 315800, People's Republic of China.
Background:
Acute kidney injury (AKI) is a critical clinical syndrome with high morbidity and mortality, primarily driven by mitochondrial oxidative stress and tubular epithelial cell apoptosis. Current antioxidant therapies are limited by poor bioavailability and lack of renal specificity. To address this, we developed a dual-targeting nanomedicine based on ultrasmall chitosan oligosaccharide-functionalized ruthenium-curcumin nanodots (LMWC/Ru-Cur).
Methods:
Ru-Cur coordination polymer nanodots were synthesized and subsequently coated with low-molecular-weight chitosan (LMWC). The nanoparticles were characterized for size, surface charge, stability, and antioxidant capacity. In vitro studies using HK-2 cells assessed cytocompatibility, cellular uptake, and protection against H2O2- or cisplatin-induced injury via measurements of viability, mitochondrial ROS, membrane potential, and apoptosis. In vivo efficacy and biodistribution were evaluated in murine models of ischemia-reperfusion- and cisplatin-induced AKI.
Results:
The resulting LMWC/Ru-Cur nanodots exhibited uniform size (~7.6 nm), good aqueous stability, and potent broad-spectrum radical scavenging ability. They were efficiently internalized by renal tubular cells via megalin receptor-mediated endocytosis, leading to significantly enhanced renal accumulation. Treatment with LMWC/Ru-Cur attenuated oxidative stress, restored mitochondrial function, reduced apoptosis in injured HK-2 cells, and improved renal function (serum creatinine and blood urea nitrogen), histopathology, and inflammatory cytokine levels in both AKI models, outperforming free curcumin or unmodified Ru-Cur. The nanodots also demonstrated favorable short-term biocompatibility and in vivo biosafety.
Conclusion:
LMWC/Ru-Cur nanodots represent a promising targeted nanotherapeutic strategy for AKI, integrating passive glomerular filtration with active receptor-mediated tubular delivery to effectively mitigate oxidative stress and mitochondrial damage, thereby preserving renal function. This work provides a rational design for metal-polyphenol based nanomedicines in the treatment of acute organ injury.
Insights
New nanomedicine using ruthenium-curcumin nanodots (LMWC/Ru-Cur) effectively treats acute kidney injury (AKI) by reducing oxidative stress and apoptosis. This targeted approach enhances renal accumulation and improves kidney function in preclinical models.
Area of Science:
- Biomedical Engineering
- Nanomedicine
- Renal Physiology
Background:
- Acute kidney injury (AKI) is a severe condition with high mortality, often caused by mitochondrial oxidative stress and cell apoptosis.
- Existing antioxidant treatments for AKI have limitations in bioavailability and kidney-specific targeting.
Purpose of the Study:
- To develop and evaluate a novel dual-targeting nanomedicine, LMWC/Ru-Cur, for improved treatment of AKI.
- To investigate the efficacy of LMWC/Ru-Cur in mitigating oxidative stress and apoptosis in renal tubular cells.
Main Methods:
- Synthesized ruthenium-curcumin coordination polymer nanodots coated with chitosan (LMWC/Ru-Cur).
- Characterized nanoparticle properties (size, stability, antioxidant capacity).
- Assessed in vitro cytocompatibility, cellular uptake, and protection against AKI-inducing agents in HK-2 cells.
- Evaluated in vivo efficacy and biodistribution in murine models of AKI.
Main Results:
- LMWC/Ru-Cur nanodots (~7.6 nm) showed high stability and potent radical scavenging.
- Nanoparticles were efficiently internalized by renal tubular cells, leading to enhanced renal accumulation.
- LMWC/Ru-Cur treatment attenuated oxidative stress, restored mitochondrial function, reduced apoptosis, and improved renal function in AKI models.
- Demonstrated favorable biocompatibility and biosafety in vivo.
Conclusions:
- LMWC/Ru-Cur nanodots offer a promising targeted nanotherapeutic strategy for AKI.
- The dual-targeting approach (glomerular filtration and receptor-mediated uptake) effectively reduces oxidative stress and preserves renal function.
- This study provides a rational design for metal-polyphenol nanomedicines for acute organ injury treatment.
