NIR-II Light-Controlled Photosynthetic Activation via an Upconversion Nanoplatform for Targeted Bioenergetic Therapy in Acute Kidney Injury

Abstract

Acute kidney injury (AKI) causes renal tubular damage, driven primarily by mitochondrial dysfunction and reactive oxygen species (ROS)-mediated oxidative stress, leading to a cellular energy crisis. The physiological architecture of the kidney hampers targeted drug delivery, rendering metabolic restoration a therapeutic challenge. To address this, we developed a second near-infrared (NIR-II) light-driven, bioenergetic nanoplatform (UCTR) that leverages upconversion nanoparticle (UCNPs)-enhanced photosynthesis for energy replenishment and mitochondrial repair in AKI. The UCTR consists of thylakoid membrane (TM)-encapsulated UCNPs cloaked with activated renal tubular epithelial cell membranes (RECM), enabling targeted accumulation in injured tubules. The UCNPs convert deep-tissue-penetrating NIR-II light into visible wavelengths, activating photosynthetic adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH) synthesis within the TM component under irradiation. This exogenous bioenergetic supply mitigates hypoxia-induced mitochondrial energy deficits, while the AMPK/PGC-1α pathway is simultaneously activated to restore the mitochondrial membrane potential. Moreover, UCTR synergizes the antioxidative and anti-inflammatory effects of plantain, accelerating tubular repair.