Prediction of Drug-Induced Nephrotoxicity with a Hydroxyl Radical and Caspase Light-Up Dual-Signal Nanoprobe

Abstract

The development of well-designed nanoprobes for specific imaging of multiple biomarkers in renal cells will afford beneficial information related to the transmutation process of drug-induced kidney injury (DIKI). However, the most reported nanoprobes for DIKI detection were dependent on single-signal output and lack of kidney targeting. In this work, we reported a renal cell targeting and dual-signal nanoprobe by encapsulating Brite 670 and Dabcyl-KFFFDEVDK-FAM into a low molecular weight chitosan nanoparticle. Confocal fluorescence imaging results demonstrated that the nanoprobe could visualize the upregulation of hydroxyl radical in early stage and activation of caspase-3 in late stage of DIKI at both the renal cell and tissue level. In a mouse DIKI model, the positive time of 8 h using nanoprobe imaging was superior to that of 72 h for serum creatinine or blood urea nitrogen, 16 h for cystatin-C, and 24 h for kidney injury molecule-1 with conventional methods. These results demonstrated that the nanoprobe may be a promising tool for effective early prediction and discriminative imaging of DIKI.

Oxygen‐derived free radicals: Production, biological importance, bioimaging, and analytical detection with responsive luminescent nanoprobes

“…114,115 Conjugating these molecules to fluorescent nanoparticles, ratiometric probes for fluorescent detection of •OH were then developed. 116 For example, Zhuang et al reported an AuNC@HPF probe for •OH detection in PBS buffer and living cells. 117 AuNC@HPF probe was developed by conjugating HPF to bovine serum albumin (BSA) protected AuNCs.…”

Multifunctional titanium phosphate nanoparticles for site-specific drug delivery and real-time therapeutic efficacy evaluation

“…Recently, more and more attention has been paid to multifunctional nanocarriers that are not only used to deliver drugs to disease sites, but also to assess the therapeutic effects of the released drugs. 32,33 It is believed that real-time and noninvasive methods to evaluate the treatment efficacy will be beneficial for medical staff to know the patient well and control the drug dosage.…”

Bright and Renal-Clearable Au Nanoclusters with NIR-II Excitation and Emission for High-Resolution Fluorescence Imaging of Kidney Dysfunction

“…11 However, the sensitivity of these methods is poor because the content of these renal filtration markers may remain in the normal range even under conditions where more than 50% glomerular filtration function is lost. 12 Renal biopsy is another clinical method to identify kidney dysfunction, yet its sampling is often difficult and can cause potential damage or other complications of the kidney. 13 As such, noninvasive in vivo imaging techniques have become an attractive method to monitor kidney dysfunction in living organisms.…”

“…At present, clinical assessment of kidney function is mainly implemented by the measurement of endogenous renal filtration markers in the blood, such as blood urea nitrogen (BUN) and creatinine (CREA) . However, the sensitivity of these methods is poor because the content of these renal filtration markers may remain in the normal range even under conditions where more than 50% glomerular filtration function is lost . Renal biopsy is another clinical method to identify kidney dysfunction, yet its sampling is often difficult and can cause potential damage or other complications of the kidney .…”