Dual-Responsive Curcumin-Loaded Nanoparticles for the Treatment of Cisplatin-Induced Acute Kidney Injury

Abstract

Acute kidney injury (AKI) has been a global public health concern leading to high patient morbidity and mortality in the world. Nanotechnology-mediated antioxidative therapy has facilitated the treatment of AKI. Herein, a hierarchical curcumin-loaded nanodrug delivery system (NPS@Cur) was fabricated for antioxidant therapy to ameliorate AKI. The nanoplatform could respond to subacidic and reactive oxygen species (ROS) microenvironments. The subacidic microenvironment led to a smaller size (from 140.9 to 99.36 nm) and positive charge (from −4.9 to 12.6 mV), contributing to the high accumulation of nanoparticles. An excessive ROS microenvironment led to nanoparticle degradation and drug release. In vitro assays showed that NPS@Cur could scavenge excessive ROS and relieve oxidative stress in H2O2-induced HK-2 cells through reduced apoptosis, activated autophagy, and decreased endoplasmic reticulum stress. Results from cisplatin-induced AKI models revealed that NPS@Cur could effectively alleviate mitochondria injury and protect kidneys via antioxidative protection, activated autophagy, decreased endoplasmic reticulum stress, and reduced apoptosis. NPS@Cur showed excellent biocompatibility and low toxicity to primary tissues in mice. These results revealed that NPS@Cur may be a potential therapeutic strategy for efficiently treating cisplatin or other cause-induced AKI.

Natural products applied in acute kidney injury treatment: polymer matters

“…7) via the assembly of two individual copolymers, one was the block-polymer of PEG and polyacrylic esters with grafted alginic acid (AGA), named PEG- b -PAGA, and the other was the random copolymer of polyacrylic esters with phenylboronic acid and 2-(dimethylamino)ethyl groups (PDMAEMA- r -PAAPBA). 86 The fabricated nanoparticles were shelled by negatively charged PEG- b -PAGA, and the boronate ester formed between phenylboronic acid and AGA could respond to both ROS and acidic microenvironment and present a positively charged sub-shell of PDMAEMA. The switch of surface charge could prolong the circulation period and enrich the accumulation in cisplatin injured renal tissues.…”

ROS-responsive curcumin-encapsulated nanoparticles for AKI therapy via promoting lipid degradation in renal tubules

“…The samples were incubated at 37 1C for 72 h, and the particle size was measured every 12 h. The degradation of NPS BG in response to ROS was investigated using the Nile red fluorescence assay, following the methodology of the previous study. 15 The solution of NPS BG was mixed with Nile red at the final concentration of 1 Â 10 À6 mol L À1 . The mixture was ultrasonicated for 30 min at 25 1C to incorporate the Nile red dye into the polymeric nanoparticles.…”

“…4-Hydroxyphenylboronic acid pinacol ester (PBAE), a derivative of benzene boronic acid, responded specifically to hydrogen peroxide (H 2 O 2 ) degradation, a prominent ROS at the pathological level. 15,27,28 Therefore, PBAE-based polymers can be used as the ROS-responsive factor to design drug delivery systems in the oxidative stress microenvironment characteristic of AKI.…”

“…Autophagy activation by Cur has been found to protect against oxidative stress, inflammation, and apoptosis in AKI. 15 Additionally, Cur has been observed to reduce lipid accumulation by reducing fatty acid synthesis and increasing fatty acid oxidation in obesity. 16 However, research on Cur's role in lipophagy in AKI is currently limited, and further studies are needed to better understand whether Cur promotes lipophagy to alleviate AKI.…”

Nanomedicine in kidney disease

“…Gold nanoclusters capped with NAC demonstrated improved antioxidative and anti-inflammatory effects compared with free NAC, achieving AKI reduction and reduced rodent mortality [19 ▪ ]. Several other substances that were traditionally known to act as antioxidants have been loaded into nanoparticles targeted to RTEC, successfully reducing oxidative stress in the injured kidney and mitigating kidney dysfunction [20 ▪ –26 ▪ ]. A promising strategy has been to co-load within nanocarriers both ROS scavengers along with drugs used to treat other damage mechanisms to further reduce inflammation [27 ▪▪ ] or intracellular calcium, which is believed itself to trigger multiple damage mechanisms [28 ▪▪ ].…”