Nanomedicine-based treatment:An emerging therapeutical strategy for pulmonary hypertension

Pulmonary hypertension(PH)can cause breathing difficulty,a rapid decline of exercise capacity,heart failure,eventually death of the patients.The latest epidemiological study demonstrates that PH has a much higher incidence than previously thought.PH is still a highly fatal disease due to the many disadvantages of the current drugs,such as short half-life,lack of targeting,potent side effects.The PH pathological features offer great opportunities for nanomedicines for PH.Recently,emerging nanomedicines demonstrated great advantages in the therapeutic effect of PH by enhancing the accumulation of drugs in PH lesion,optimizing drug efficacy,minimizing drug side effects.However,this promising field of cross-cutting research is far from being widely explored due to the huge professional barriers.To solve this problem,we provide a comprehensive review for the latest progresses of nanomedicines in the treatment of PH.Firstly,we systematical summarized the PH pathological features and the current clinical drug treatment of PH.The advantages of nanomedicines are also deeply discussed in the treatment of PH.Subsequently,we focused on the research progresses of nanomedicines in PH through three aspects:advanced nano-drug delivery system for traditional drugs and new target drugs,gene therapy-based nanomedicines,other nanomedicines for the treatment of PH.Finally,we also discussed the prospects and challenges for the clinical application of nanomedicines in PH,provided directions for the research and development of nanomedicines for PH treatment in the future.

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.

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.