(K-431) ROS scavenging bio-origniated nanozyme and its effect on acute kidney injury

Saturday, October 14, 2023

9:30 AM – 10:30 AM PDT

Location: Exhibit Hall - Row K - Poster # 431

Presenting Author(s)

KM

Kiyoon Min (she/her/hers)

MS/PhD integrated student
Gwangju Institute of Science and Technology
Gwangju, United States

Co-Author(s)

AS

Abhishek Sahu

Professor
National Institute of Pharmaceutical Education & Research (NIPER), United States
SJ

Saehyun Jeon

Master student
Gwangju Institute of Science and Technology, United States

Primary Investigator(s)

GT

Giyoong Tae

Professor
Gwangju Institute of Science and Technology, United States

Introduction::

Intracellular antioxidant systems control intracellular reactive oxygen species (ROS) for homeostasis in organisms. However, excess ROS and high oxidative stress in inflammatory environments devour the cellular antioxidant defense systems. Consequently, various biomaterials that can scavenge ROS have been actively studied as therapeutics for inflammatory diseases. Nanozymes, primarily metal- and inorganic-based, have garnered attention as ROS-scavenging nanomedicines due to their enzyme-mimetic activities, high stability, inexpensiveness, and ease of chemical modification. However, their long-term biocompatibility and biosafety in vivo remain controversial. Therefore, in this study, we developed a biodegradable and bio-originated nanozyme system by conjugating henin to a biopolymer to form self-assembled nanoparticles. Dual enzymatic activities and cascade reaction of the novel nanozyme system and its cellular protective effect under high oxidative stress was investigated. Furthermore, the therapeutic effect of the nanozyme was evaluated using a mouse model of acute kidney injury.

Materials and Methods:: Hemin was chemically conjugated to a biopolymer. Superoxide dismutase (SOD)- and catalase (CAT)-mimetic activities, as well as its cascade reaction activity, were measured using xanthine/xanthine oxidase system and oxygen measurement, respectively. The cellular protective effect in a hydrogen peroxide (H₂O₂) condition was evaluated using a kidney proximal tubule cell line. An in vivo acute kidney failure model was established by intramuscular injection of glycerol after water restriction. The biodistribution of the nanozyme was investigated by ex vivo fluorescent imaging. The therapeutic effects on the acute kidney failure were analyzed through serum and tissue analyses 24 hr after intravenous administration of the nanozyme.

Results, Conclusions, and Discussions:: Hemin was successfully conjugated to a biopolymer, resulting in nano-sized self-assembled particles and enhanced colloidal stability in the physiological environment. The nanozyme exhibited higher ROS scavenging activities compared to hemin itself (Fig. 1A), and it could effectively protect proximal tubule cells in an H₂O₂ environment, even at a low concentration (1 μM) (Fig. 1B). The nanozyme also revealed an excellent targeting efficiency selectively towards injured kidneys, showing higher accumulation compared to the normal kidneys by the enhanced penetration through the damaged glomerulus. The nanozyme mitigated the serum BUN and creatinine levels in acute kidney failure-induced mice (Fig. 1C), along with reduced ROS levels (DHE) (Fig. 1D) and apoptotic cells in inflamed tissues. Furthermore, they alleviated the expression of kidney injury molecule-1 (KIM-1) (Fig. 1D) as well as macrophage and pro-inflammatory cytokine in the kidneys. Therefore, bio-originated, thus biocompatible nanozyme with high catalytic activities can serve as a safe and stable substitute for other nanozymes and natural enzymes.

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