Polyphosphate- and Antioxidant Peptide-Based Coacervate Delivers miRNA

Area of Science:

• Biomaterials Science
• RNA Therapeutics
• Cellular Delivery Systems

Background:

• RNA-based therapies face challenges with stability and efficient delivery to the cytoplasm.
• Liquid-liquid phase separation (LLPS) forms coacervate droplets, showing potential for biomacromolecule delivery.
• Antioxidant peptides and polyphosphates are explored for therapeutic applications.

Purpose of the Study:

• To develop a novel coacervate artificial cell for improved microRNA delivery.
• To enhance RNA stability and cytoplasmic delivery efficiency for therapeutic applications.
• To evaluate the therapeutic potential of these coacervate systems in an acute lung injury model.

Main Methods:

• Formation of coacervate droplets via LLPS of sodium hexametaphosphate (SHMP) and antioxidant peptide SS-31.
• Loading of microRNA-223 into coacervate droplets to form Coac@miR.
• Coating Coac@miR with erythrocyte membranes (EMCoac@miR) for enhanced stability.
• In vitro assessment of cytoplasmic delivery efficiency and in vivo evaluation in an acute lung injury mouse model.

Main Results:

• Coacervate artificial cells demonstrated a 10-fold increase in cytoplasmic delivery efficiency of miRNA-223 compared to miRNA-223 alone.
• Intratracheal and intravenous administration of the coacervate systems alleviated acute lung injury in mice.
• Treatment reprogrammed macrophages to an anti-inflammatory (M2) phenotype, reduced inflammatory factors, and mitigated ROS stress.

Conclusions:

• PolyP-peptide-based coacervate artificial cells represent a novel and effective delivery system for miRNAs.
• Erythrocyte membrane coating enhances RNA protection against degradation.
• These coacervate systems hold therapeutic potential for immune-related and inflammatory diseases.