Kidney-Targeted Biomimetic Nanoparticles Loaded With Apolipoprotein H Alleviate Sepsis-Associated Acute Kidney Injury...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Renal Medicine

Background:

• Sepsis-associated acute kidney injury (SA-AKI) presents high mortality and limited treatment options.
• Current therapies lack efficient kidney targeting, leading to poor efficacy.
• Recombinant apolipoprotein H (rAPOH) shows therapeutic potential but suffers from poor targeting and rapid clearance.

Purpose of the Study:

• To develop a biomimetic nanocarrier for targeted delivery of rAPOH to treat SA-AKI.
• To evaluate the efficacy and mechanism of the KMA@rAPOH system in vitro and in vivo.

Main Methods:

• Construction of a biomimetic nanocarrier (KMA@rAPOH) using cell membranes and rAPOH.
• In vitro assessment of cellular uptake, anti-apoptotic, and anti-inflammatory effects.
• In vivo evaluation in a mouse model of SA-AKI, including pathological analysis and immune cell profiling.
• Mechanistic studies involving TLR4/NF-κB signaling pathway analysis.

Main Results:

• KMA@rAPOH demonstrated efficient drug loading, controlled release, and stability.
• In vitro studies showed efficient internalization and significant anti-apoptotic/anti-inflammatory effects in renal cells.
• In vivo, KMA@rAPOH alleviated renal damage, reduced apoptosis, and modulated pro-inflammatory macrophage populations.
• The nanocarrier inhibited the TLR4/NF-κB pathway, decreasing pro-inflammatory cytokine secretion.

Conclusions:

• The KMA@rAPOH biomimetic nanoplatform enables targeted delivery of rAPOH for SA-AKI therapy.
• This system shows significant renoprotective effects by reducing inflammation and apoptosis.
• The findings highlight a promising targeted nanodelivery strategy for renal inflammatory disorders.