Sequential Therapy of Acute Kidney Injury with a DNA Nanodevice

Abstract

The high demand for acute kidney injury (AKI) therapy calls the development of multifunctional nanomedicine for renal management with programmable pharmacokinetics. Here, we developed a renal-accumulating DNA nanodevice with exclusive kidney retention for longitudinal protection of AKI in different stages in a renal ischemia-reperfusion (I/R) model. Due to the prolonged kidney retention time (>12 h), the ROS-sensitive nucleic acids of the nanodevice could effectively alleviate oxidative stress by scavenging ROS in stage I, and then the anticomplement component 5a (aC5a) aptamer loaded nanodevice could sequentially suppress the inflammatory responses by blocking C5a in stage II, which is directly related to the cytokine storm. This sequential therapy provides durable and pathogenic treatment of kidney dysfunction based on successive pathophysiological events induced by I/R, which holds great promise for renal management and the suppression of the cytokine storm in more broad settings including COVID-19.

Radiolabeling and Preliminary Evaluation of 99mTc-Labeled DNA Cube Nanoparticles as Potential Tracers for SPECT Imaging

“…DNA nanostructures, with the advantages of structural designability and spatial addressability, have shown a great potential in the field of biosensing, 10−12 drug delivery, [13][14][15] and bio-medicine. [16][17][18][19] DNA cube nanoparticles (DCN), 20 a classic example of DNA nanostructures, could be readily assembled with 6 designed DNA oligonucleotides. To successfully prepare DCN, we designed a set of six short oligonucleotides for self-assembly, and the results supported our establishment of DCN.…”

Smart Drug Delivery Systems Based on DNA Nanotechnology

“…Further, Ge et al. developed a functional DNA nanodevice for sequential therapy of AKI by loading anticompletment component 5a (aC5a) aptamer onto rectangular DNA origami [116] . At stage I (first 8 h), the DNA origami scaffold could efficiently scavenge ROS to alleviate acute kidney injury, and then aC5a aptamers on DNA origami competitively bound to C5a to suppress inflammatory response at stage II.…”

Therapeutic Applications of Programmable DNA Nanostructures

“…Rectangular DNA origami showed renoprotective properties with efficacy similar to a clinically used drug. A similar approach in the therapy of acute kidney injury was recently adapted by Chen et al where they applied rectangular DONs (rDONs) by upgrading as a nanodevice with anti-C5a aptamers (aC5a) to block the C5a-mediated inflammation [129]. aC5a-rDONs allowed for the local protection from oxidative stress by scavenging ROS in stage I and suppress the inflammatory responses by blocking C5a in stage II in a renal ischemia-reperfusion (I/R model).…”