Prediction of Drug-Induced Nephrotoxicity with a Hydroxyl Radical and Caspase Light-Up Dual-Signal Nanoprobe.
Yuling TongXitong HuangMi LuBo-Yang YuJiangwei TianPublished in: Analytical chemistry (2018)
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.
Keyphrases
- drug induced
- fluorescence imaging
- liver injury
- living cells
- induced apoptosis
- high resolution
- early stage
- photodynamic therapy
- single cell
- cell death
- cell therapy
- adverse drug
- fluorescent probe
- endoplasmic reticulum stress
- stem cells
- metabolic syndrome
- poor prognosis
- signaling pathway
- oxidative stress
- cell cycle arrest
- quantum dots
- bone marrow
- rectal cancer
- electronic health record
- hyaluronic acid
- long non coding rna
- loop mediated isothermal amplification