Drug Molecule Recruitment Empowered by Phase Separation on Cell Membranes In Vivo

Area of Science:

• Biomolecular Engineering
• Nanomedicine
• Cellular Biology

Background:

• Phase-separated coacervates are crucial for cellular compartmentalization and regulation.
• Harnessing phase separation for in vivo therapeutic delivery is challenging but promising.

Purpose of the Study:

• To develop and validate a novel in vivo phase separation system for targeted anticancer drug delivery.
• To enhance drug internalization and therapeutic efficacy using cell membrane-based coacervates.

Main Methods:

• Development of a Phase Separation Enhanced Drug Delivery System (PEDS) utilizing drug-conjugated and targeting peptides.
• Demonstration of in situ co-phase separation on cancer cell membranes in vivo.
• Evaluation of cellular internalization, tumor accumulation, and off-target organ deposition.

Main Results:

• In situ co-phase separation significantly enhanced cellular internalization of drug-conjugated peptides.
• PEDS demonstrated selective accumulation at tumor sites.
• Minimal drug deposition was observed in off-target organs like the liver and kidneys, unlike conventional nanomedicines.

Conclusions:

• Phase separation is a powerful tool for in vivo therapeutic applications, particularly in targeted drug delivery.
• PEDS offers a novel strategy for enhancing anticancer drug efficacy and minimizing systemic toxicity.
• This approach provides new insights into leveraging biomimetic phase separation for advanced drug delivery systems.