Innovative integration of plant photosynthetic system for targeted restoration of NAD+/NADPH imbalance in acute kidney injury

Abstract

Acute kidney injury (AKI) is a serious and highly prevalent disease that currently relies heavily on supportive treatment (such as dialysis and fluid management) in clinical practice. However, research on its fundamental pathological mechanisms has revealed more specific treatment pathways. Based on two innovative studies by Pengfei Chen et al. (published in Nature in 2022) and Yao Lei et al. (published in Nature Biomedical Engineering in 2025), this article integrates their core content to summarize a groundbreaking metabolic regulation strategy. Pengfei Chen et al. developed an independent controllable photosynthetic system based on nano encapsulated chloroplast units (NTU), which provides key energy carriers ATP and metabolic reducing carriers NADPH in situ through photoactivation, effectively correcting energy imbalance in degenerated chondrocytes, restoring cellular metabolic homeostasis, and inhibiting the pathological progression of osteoarthritis; Its cross species membrane modification optimization ensures biocompatibility and stability. Yao Lei et al. further developed an ultrasound responsive liposome system that integrates vesicular chloroplast fragments and encapsulates L-ascorbic acid for the treatment of AKI. After intravenous injection, liposomes target and accumulate in the proximal tubular cells of the damaged kidney. Quinolinate phosphoribosyltransferase expressed in chlorophyll is used to catalyze NAD+ synthesis, and local ultrasound activation is used to promote electron transfer of ascorbic acid to form NADH, restore ATP levels, enhance the pentose phosphate pathway to generate NADPH, reduce reactive oxygen species (ROS) levels, and ultimately restore energy supply and antioxidant capacity of renal tubular cells, achieving renal function recovery and injury prevention in the AKI model. These two studies jointly demonstrate a precise metabolic enhancement strategy based on the principle of photosynthesis, targeting the repair of energy imbalance and mitochondrial dysfunction by providing key metabolites such as ATP, NADPH, and NAD+, opening up a new biological therapy pathway for the treatment of AKI.