Renal Clearable Quantum Dot-Drug Conjugates Modulate Labile Iron Species and Scavenge Free Radicals for Attenuating Chemotherapeutic Drug-Induced Acute Kidney Injury.
Zitong ZhuXinchen LiuPenghui LiHuan WangYanjie ZhangMengmeng LiuJinsong RenPublished in: ACS applied materials & interfaces (2023)
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.
Keyphrases
- drug induced
- acute kidney injury
- liver injury
- cell death
- reactive oxygen species
- cardiac surgery
- cell cycle arrest
- dna damage
- oxidative stress
- adverse drug
- emergency department
- iron deficiency
- quantum dots
- endoplasmic reticulum stress
- physical activity
- weight gain
- type diabetes
- cancer therapy
- body mass index
- weight loss
- depressive symptoms
- anti inflammatory