Oral PTP1B siRNA Delivery Using Milk-Derived Extracellular Vesicles for Alleviation of Acute Kidney Injury

Area of Science:

• Nephrology
• Biomedical Engineering
• Molecular Biology

Background:

• Acute kidney injury (AKI), often due to ischemia-reperfusion (IR), lacks effective treatments.
• AKI pathology involves oxidative stress, endoplasmic reticulum (ER) stress, and inflammation.
• Protein tyrosine phosphatase 1B (PTP1B) inhibition is a potential therapeutic strategy for ischemic diseases.

Purpose of the Study:

• To investigate PTP1B overexpression in AKI.
• To evaluate the therapeutic efficacy of PTP1B-targeting siRNA (PTPi) delivered by milk-derived extracellular vesicles (mEVs) for AKI treatment.

Main Methods:

• Assessed PTP1B levels in AKI patient and mouse tissues.
• Developed PTPi-loaded mEVs (PTPi@mEVs) for targeted delivery.
• Administered PTPi@mEVs to IR-AKI mouse models, including oral administration.

Main Results:

• PTP1B was overexpressed in AKI tissues, correlating with ER stress and inflammation.
• PTPi@mEVs reduced PTP1B expression, ER stress, Src activation, and inflammation in vitro.
• In vivo, PTPi@mEVs improved renal function, reduced cell death, and preserved kidney structure in IR-AKI mice.

Conclusions:

• PTP1B is a viable therapeutic target for AKI.
• mEVs serve as an effective delivery system for siRNA targeting PTP1B.
• Targeting the ER stress-oxidative stress-inflammatory axis via PTP1B inhibition shows promise for AKI treatment.