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

Abstract

Acute kidney injury (AKI) is a life-threatening clinical syndrome characterized by metabolic imbalance of renal proximal tubular cells (PTCs), including ATP depletion, nicotinamide adenine dinucleotide (NAD+) deficiency, and NADPH exhaustion, and current therapies such as NAD+ precursors fail to address this multi-target metabolic disorder. This highlight integrates two innovative plant photosynthesis-based systems—nanothylakoid units coated with chondrocyte membranes (CM-NTU, Chen et al., Nature, 2022, 612, 546–554) and ultrasound-responsive thylakoid-integrating liposomes (LipTk-AA, Lei et al., Nat Biomed Eng., 2025, 9(10), 1740–1757)—to propose a synergistic fused platform that overcomes the limitations of individual systems. By combining CM-NTU's modular membrane camouflage and light-driven NADPH/ATP production with LipTk-AA's ultrasound deep-tissue activation and NAD+ de novo synthesis, the fused system achieves precise targeting, spatiotemporal control, and comprehensive metabolic repair encompassing ATP, NAD+, and NADPH; we elaborate on their metabolic cross-talk, material design, and clinical translation prospects, highlighting how this fusion drives the field of metabolic-regulatory therapy beyond single-system capabilities.