Renal Clearable Quantum Dot–Drug Conjugates Modulate Labile Iron Species and Scavenge Free Radicals for Attenuating Chemotherapeutic Drug-Induced Acute Kidney Injury

Abstract

Chemotherapeutic drug-induced acute kidney injury (AKI) involves pathologically increased labile iron species in the kidneys that mediate the excessive generation of reactive oxygen species (ROS) to induce ferroptosis and apoptosis, subsequently driving renal dysfunction. Herein, we report renal clearable quantum dot−drug conjugates (QDCs) composed of carbon quantum dot (CDs), deferoxamine (DFO), and poly(ethylene glycol) (PEG) for attenuating chemotherapeutic drug-induced AKI. The CDs component in QDCs can not only provide DFO with high renal specificity to effectively remove the pathological labile iron species in the kidneys to block the source of ROS generation but also exert high antioxidative effects to avoid renal oxidative damage caused by the ROS that have been overproduced. In cisplatin-induced AKI mice, QDCs can inhibit ferroptosis and apoptosis with high efficacy for AKI treatment. This study will provide a new paradigm to realize enhanced therapeutic efficacy for AKI by simultaneously removing the pathological labile iron species and eliminating overproduced ROS in the kidneys to achieve the goal of addressing both symptoms and root causes.

Molecular Mechanisms of Ferroptosis and Their Involvement in Acute Kidney Injury

“…By constructing a quantum dot-drug conjugate compounded with carbon quantum dots, desferrioxamine, and polyethylene glycol, the researchers not only effectively scavenged excess intracellular Fe2+ and avoided the overproduction of ROS, but also had good efficacy in treating mice from CP-AKI. 88 , 89 Recent studies have found that dioscin can reduce the oxidative damage, apoptosis, and ferroptosis of the kidney through Nrf2/HO-1 signaling pathway, and play a protective role on CP-AKI. 90 Qi et al 91 found that CP-AKI was associated with an imbalance of ferritin metabolism in proximal tubular cells, and that administration of inositol promoted Hsc-70-interacting protein-mediated NOX4 ubiquitination, which effectively inhibited ferroptosis and improved CP-AKI.…”

A bimetallic nanozyme coordinated with quercetin for efficient radical scavenging and treatment of acute kidney injury

“…20–26 In addition, various antioxidant nanozymes have demonstrated promising effectiveness in the management of AKI. These nanozymes encompass metal complexes, 3,27–30 carbon dots, 31–33 and DNA origami. 34–37 Nanozymes offer significant advantages in enhancing bioavailability and exhibit significant potential in the therapeutic management of AKI.…”

Targeted inhibition of pyroptosis via a carbonized nanoinhibitor for alleviating drug-induced acute kidney injury

“…22–25 Besides, ultrasmall nanocarbons with proper sizes and structures can exhibit prolonged body retention and kidney-targeting ability. 24,26,27 Inspired by the aforementioned characteristics, we envisioned that the integration of the pyroptosis inhibitory activity into nanocarbons may bring unexpected outcomes in AKI treatment. In this study, we present the design and construction of a pharmacologically active carbonized nanoinhibitor (P-RCDs) derived from a molecular pyroptosis inhibitor, 3,4′,5-trihydroxystilbene, for attenuating chemotherapeutic drug-induced AKI (Fig.…”