Stability-Enhanced Therapeutic Artificial Cells Based on a Lipid-Polymer Integrated Architecture

Area of Science:

• Biomaterials Science
• Synthetic Biology
• Nanotechnology

Background:

• Current artificial cells struggle with physiological robustness and rely on biological methods for cargo exchange.
• Mimicking natural cell functions like cargo exchange often requires complex biological components.

Purpose of the Study:

• To design and construct robust artificial mini cells (MCs) with a novel lipid-polymer integrated architecture.
• To achieve controllable metabolic reactions and convenient surface functionalization for biomedical applications.

Main Methods:

• Constructed MCs using a lipid-polymer integrated architecture with a cross-linked zwitterionic polymer as a cytoskeleton mimic.
• Incorporated azobenzene-gated lipids as light-responsive channel protein mimics for regulating membrane permeability.
• Designed therapeutic MCs (aPDL1-Tt-MC(GOx + Cat)) with tumor tropism and encapsulated glucose oxidase-catalase (GOx-Cat) system.

Main Results:

• The lipid-polymer architecture provided robust structural stability and facilitated surface functionalization.
• Light-responsive lipids enabled spatiotemporal control over membrane permeability and metabolic reactions.
• The proof-of-concept therapeutic MCs demonstrated tumor tropism and enhanced antitumor efficacy via PD-1/PD-L1 blockade and controlled oxygen generation.

Conclusions:

• The developed artificial mini cells offer a promising platform for robust and controllable biomedical applications.
• The rational chemical design strategy overcomes limitations of existing artificial cell technologies.
• These advanced artificial cells hold potential for targeted cancer therapy and other biomedical interventions.