Reflecting recent work in the Deming Lab

Self-assembled polymeric vesicles that respond to biologically relevant stimuli have significant potential in drug delivery and synthetic biology. While many stimuli-responsive assemblies disassemble upon activation, invertible vesicles offer a unique advantage: they not only release cargo but can also encapsulate new material upon inversion. Published in the Journal of the American Chemical Society, researchers in the Deming Lab at the Department of Bioengineering, University of California, at Los Angeles, introduce amphiphilic diblock copolypeptide vesicles that undergo vesicle-to-vesicle inversion under biologically relevant conditions through a single thiol stimulus.

From Left: First author, Casey A. Morrison, and Timothy J. Deming, PI

The lab members designed MOxADHy block copolypeptides that self-assemble into stable vesicles in water at physiological conditions – pH 7.4, 37°C, 150 mM NaCl. These vesicles incorporate poly(l-methionine sulfoxide), MO, as a hydrophilic domain and poly(dehydroalanine), ADH, as a hydrophobic domain, allowing reversible amphiphilicity switching. Upon reaction with thiols such as glutathione, GSH, or thioglycolic acid, TGA, MO is converted into hydrophobic poly(l-methionine), M, while ADH is transformed into hydrophilic poly(S-alkyl-rac-cysteine), CrR.

This transformation triggers vesicle inversion, enabling controlled cargo release and potential re-encapsulation. Unlike previous systems requiring extreme conditions, this inversion occurs under mild, biologically relevant conditions. Notably, TGA-triggered inversion allows partial retention of encapsulated cargo, demonstrating potential for biomimetic applications in controlled drug release and uptake.

This work establishes a biocompatible, enzyme-degradable, and reversible vesicle system, offering new possibilities for targeted drug delivery, encapsulation of biological fluids, and synthetic cell-mimicking architectures. The ability to trigger vesicle inversion under physiological conditions provides an innovative tool for next-generation biomaterials and therapeutics.