Comparison of iohexol and iodixanol induced nephrotoxicity, mitochondrial damage and mitophagy in a new contrast-induced acute kidney injury rat model

Part & Part Syst Charact

et al. 2019

Photothermal therapy (PTT) is an emerging noninvasive and precise localized therapeutic modality; however, it is deeply limited by its poor tumor accumulation, inadequate photothermal conversion efficiency, and the thermoresistance of cancer cells. Aimed at these shortcomings, tumor‐targeting nanoparticles (iRGD‐W18O49‐17AAG) comprising carboxyl‐group‐functionalized W18O49 nanoparticles, integrin‐targeting peptide iRGD, and HSP90‐inhibitor 17AAG are developed. The W18O49 nanoparticles act as excellent PTT carriers and computed tomography (CT) imaging contrast agents. The ring type polypeptide iRGD promotes the accumulation of nanoparticles in the tumour and further penetration into cancer cells. The introduction of 17AAG can inhibit the heat‐shock response and overcome the thermoresistance, thus increasing the curative effect of PTT and reducing the chance of tumor recurrence. The W18O49 nanoparticles can also be used to monitor and guide the phototherapeutic through CT and near‐infrared fluorescence imaging after modification with Cy5.5. In addition, superior biosafety is also indicated in both preliminary in vitro and in vivo assessments. The potential of iRGD‐W18O49‐17AAG in tumor targeting, dual modality imaging‐guided and remarkable enhanced PTT of gastric cancer with ignorable side effect both in vitro and in vivo, which may be further applied in clinic, is highlighted.

Section: Resultsmentioning

confidence: 99%

Tumor‐Targeting W₁₈O₄₉ Nanoparticles for Dual‐Modality Imaging and Guided Heat‐Shock‐Response‐Inhibited Photothermal Therapy in Gastric Cancer

Yang

Wang

Part & Part Syst Charact

et al. 2019

“…The rats were divided into four groups: control group (n = 6), CI-AKI group (n = 6), CI-AKI group receiving a tail vein injection of rhSTC1 (5 μl) (n = 6, rhSTC1, 0.5 μg/rat), and CI-AKI group receiving a tail vein injection of rhSTC1 (10 μl) (n = 6, rhSTC1, 1 μg/rat). The CI-AKI rat model was built according to our previous article [6]. The rhSTC1 is a human-derived recombinant protein, but its function has been testified in other previous studies [20,21].…”

Section: Animal Experimentalmentioning

confidence: 99%

“…Ways of measuring blood urea nitrogen (BUN), serum creatinine (Scr), and renal pathology were described in our recent studies [6]. Briefly, kidney tissue was fixed and embedded, and tissue sections (4 μm thick) were then stained with hematoxylin-eosin for histopathological analysis.…”

Section: Assessment Of Renal Function and Histopathologymentioning

confidence: 99%

“…Blotting. Cells or renal cortical tissues (n = 3 from each group) were isolated, as described previously [6,7]. Nuclear and cytoplasm protein were extracted according to the operating instructions.…”

Section: Westernmentioning

confidence: 99%

“…Many pathophysiological processes contribute to the development of CI-AKI, such as renal medullary ischemia, direct tubular cytotoxicity of contrast, overproduction of reactive oxygen species (ROS), mitochondrial damage, and mitophagy [1,[6][7][8][9]. Most guidelines suggest that expanding intravascular volume is more reasonable in preventing CI-AKI [10,11].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Stanniocalcin-1 Alleviates Contrast-Induced Acute Kidney Injury by Regulating Mitochondrial Quality Control via the Nrf2 Pathway

Zhao

Feng

Oxidative Medicine and Cellular Longevity

et al. 2020

Self Cite

Contrast-induced acute kidney injury (CI-AKI) is the third common cause of acute kidney injury (AKI), which is associated with poor short- and long-term outcomes. Currently, effective therapy strategy for CI-AKI remains lacking. Stanniocalcin-1 (STC1) is a conserved glycoprotein with antiapoptosis and anti-inflammatory functions, but the role of STC1 in controlling CI-AKI is unknown. Here, we demonstrated a protective role of STC1 in contrast-induced injury in cultured renal tubular epithelial cells and CI-AKI rat models. Recombinant human STC1 (rhSTC1) regulated mitochondrial quality control, thus suppressing contrast-induced mitochondrial damage, oxidative stress, inflammatory response, and apoptotic injury. Mechanistically, activation of the Nrf2 signaling pathway contributes critically to the renoprotective effect of STC1. Together, this study demonstrates a novel role of STC1 in preventing CI-AKI and reveals Nrf2 as a molecular target of STC1. Therefore, this study provides a promising preventive target for the treatment of CI-AKI.

Renoprotective Angiographic Polymersomes

Cornel

2020

Adv Funct Materials

Computed tomography (CT) angiography is powerful for the diagnosis of vascular diseases. Unfortunately, this method usually requires a high dosage of iodinated contrast agents, which can lead to severe elevation of reactive oxygen species (ROS) levels within kidneys. This causes oxidative stress, apoptosis, and hence contrast‐induced nephropathy (CIN), a leading cause of iatrogenic renal failure, especially for patients with renal insufficiency. Herein, a route is shown to circumvent such problems with the usage of rationally designed renoprotective angiographic polymersomes (RAPs) as blood pool CT contrast agents. RAPs are biodegradable nanoparticles prepared via self‐assembly of poly(ethylene oxide)‐block‐poly(triiodobenzoic chloride‐conjugated polylysine‐stat‐phenylboronic acid pinacol ester‐conjugated polylysine) (PEO45‐b‐P[(Lys‐IBC)45‐stat‐(Lys‐PAPE)15]). The key to the efficiency of such nanoparticles as renoprotective contrast agents arises from the rationally chosen repeat units: Lys‐IBC exhibits a concentration‐dependent X‐ray attenuation capability and Lys‐PAPE introduces an ROS‐scavenging ability to the polymersome. The study shows that RAPs can reduce the risk of CIN in mice with kidney injury. Additionally, a 5‐fold increase in angiographic live time is observed using RAPs, compared to commonly used iodinated small molecule contrast agents. In summary, a new strategy is proposed for the design of a renoprotective angiographic contrast agent that is capable of reducing the risk of CIN.