Nanoparticle-delivered biosensor for reactive oxygen species in diabetes.
The cell's own antioxidant response element (ARE) can be used to evaluate the complications of diabetes mellitus. The hypothesis that a synthetic ARE could be used as a genetic switch, or biosensor, to turn on and off therapeutic genes is tested herein. Mitochondrial oxidative stress (MOS) has been hypothesized as one of the earliest insults in diabetes. Fluorescent probes used to monitor MOS revealed that the addition of glucose at physiological levels to cultures of endothelial cells was able to induce MOS above normal levels and in a dose-dependant manner. Additional data showed that increased glucose levels activated the ARE-GFP in a dose-dependant manner. These data support the hypothesis that the induction of MOS is more sensitive to hyperglycemia than the induction of the ARE. Delivery of an ARE-GFP construct with nanoparticles to the eye was successful using sub-retinal injection. This ARE-GFP/nanoparticle construct was functional and reported the activation of the ARE in diabetic rat retinal pigment epithelium (RPE). These data support the use of nanoparticle-delivered biosensors for monitoring the oxidative status of tissues in vivo.
Prow
Tarl W
TW
The University of Queensland, Australian Institute for Bioengineering and Nanotechnology, St. Lucia, Qld, Australia. uqtprow@uq.edu.au
Bhutto
Imran
I
Grebe
Rhonda
R
Uno
Koichi
K
Merges
Carol
C
McLeod
D Scott
DS
Lutty
Gerard A
GA
D000818:Animals; D015374:Biosensing Techniques; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018014:Gene Transfer Techniques; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods; D008928:Mitochondria / Q000378:metabolism; D053758:Nanoparticles; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics
D017382:Reactive Oxygen Species; D005947:Glucose