Passively-targeted mitochondrial tungsten-based nanodots for efficient acute kidney injury treatment

Acute kidney injury(AKI)can lead to loss of kidney function and a substantial increase in mortality.The burst of reactive oxygen species(ROS)plays a key role in the pathological progression of AKI.Mitochondrial-targeted antioxidant therapy is very promising because mitochondria are the main source of ROS in AKI.Antioxidant nanodrugs with actively targeted mitochondria have achieved encouraging success in many oxidative stress-induced diseases.However,most strategies to actively target mitochondria make the size of nanodrugs too large to pass through the glomerular system to reach the renal tubules,the main damage site of AKI.Here,an ultra-small Tungsten-based nanodots(TWNDs)with strong ROS scavenging can be very effective for treatment of AKI.TWNDs can reach the tubular site after crossing the glomerular barrier,and enter the mitochondria of the renal tubule without resorting to complex active targeting strategies.To our knowledge,this is the first time that ultra-small negatively charged nanodots can be used to passively target mitochondrial therapy for AKI.Through in-depth study of the therapeutic mechanism,such passive mitochondria-targeted TWNDs are highly effective in protecting mitochondria by reducing mitochondrial ROS and increasing mitophagy.In addition,TWNDs can also reduce the infiltration of inflammatory cells.This work provides a new way to passively target mitochondria for AKI,and give inspiration for the treatment of many major diseases closely related to mitochondria,such as myocardial infarction and cerebral infarction.

Nanodrugs alleviate acute kidney injury: Manipulate RONS at kidney

Currently,there are no clinical drugs available to treat acute kidney injury(AKI).Given the high prevalence and high mortality rate of AKI,the development of drugs to effectively treat AKI is a huge unmet medical need and a research hotspot.Although existing evidence fully demonstrates that reactive oxygen and nitrogen species(RONS)burst at the AKI site is a major contributor to AKI progression,the heterogeneity,complexity,and unique physiological structure of the kidney make most antioxidant and anti-inflammatory small molecule drugs ineffective because of the lack of kidney targeting and side effects.Recently,nanodrugs with intrinsic kidney targeting through the control of size,shape,and surface properties have opened exciting prospects for the treatment of AKI.Many antioxidant nanodrugs have emerged to address the limitations of current AKI treatments.In this review,we systematically summarized for the first time about the emerging nanodrugs that exploit the pathological and physiological features of the kidney to overcome the limitations of traditional small-molecule drugs to achieve high AKI efficacy.First,we analyzed the pathological structural characteristics of AKI and the main pathological mechanism of AKI:hypoxia,harmful substance accumulation-induced RONS burst at the renal site despite the multifactorial initiation and heterogeneity of AKI.Subsequently,we introduced the strategies used to improve renal targeting and reviewed advances of nanodrugs for AKI:nano-RONS-sacrificial agents,antioxidant nanozymes,and nanocarriers for antioxidants and anti-inflammatory drugs.These nanodrugs have demonstrated excellent therapeutic effects,such as greatly reducing oxidative stress damage,restoring renal function,and low side effects.Finally,we discussed the challenges and future directions for translating nanodrugs into clinical AKI treatment.

Reactive oxygen species-based nanomaterials for the treatment of myocardial ischemia reperfusion injuries

Interventional coronary reperfusion strategies are widely adopted to treat acute myocardial infarction,but morbidity and mortality of acute myocardial infarction are still high.Reperfusion injuries are inevitable due to the generation of reactive oxygen species(ROS)and apoptosis of cardiac muscle cells.However,many antioxidant and anti-inflammatory drugs are largely limited by pharmacokinetics and route of administration,such as short half-life,low stability,low bioavailability,and side effects for treatment myocardial ischemia reperfusion injury.Therefore,it is necessary to develop effective drugs and technologies to address this issue.Fortunately,nanotherapies have demonstrated great opportunities for treating myocardial ischemia reperfusion injury.Compared with traditional drugs,nanodrugs can effectively increase the therapeutic effect and reduces side effects by improving pharmacokinetic and pharmacodynamic properties due to nanodrugs’size,shape,and material characteristics.In this review,the biology of ROS and molecular mechanisms of myocardial ischemia reperfusion injury are discussed.Furthermore,we summarized the applications of ROS-based nanoparticles,highlighting the latest achievements of nanotechnology researches for the treatment of myocardial ischemia reperfusion injury.

MoS_(2)-based nanocomposites for cancer diagnosis and therapy

Molybdenum is a trace dietary element necessary for the survival of humans.Some molybdenum-bearing enzymes are involved in key metabolic activities in the human body(such as xanthine oxidase,aldehyde oxidase and sulfite oxidase).Many molybdenum-based compounds have been widely used in biomedical research.Especially,MoS_(2)-nanomaterials have attracted more attention in cancer diagnosis and treatment recently because of their unique physical and chemical properties.MoS_(2)can adsorb various biomolecules and drug molecules via covalent or non-covalent interactions because it is easy to modify and possess a high specific surface area,improving its tumor targeting and colloidal stability,as well as accuracy and sensitivity for detecting specific biomarkers.At the same time,in the near-infrared(NIR)window,MoS_(2)has excellent optical absorption and prominent photothermal conversion efficiency,which can achieve NIR-based phototherapy and NIR-responsive controlled drug-release.Significantly,the modified MoS_(2)-nanocomposite can specifically respond to the tumor microenvironment,leading to drug accumulation in the tumor site increased,reducing its side effects on non-cancerous tissues,and improved therapeutic effect.In this review,we introduced the latest developments of MoS_(2)-nanocomposites in cancer diagnosis and therapy,mainly focusing on biosensors,bioimaging,chemotherapy,phototherapy,microwave hyperthermia,and combination therapy.Furthermore,we also discuss the current challenges and prospects of MoS_(2)-nanocomposites in cancer treatment.