Janus Polymeric Giant Vesicles on Demand: A Predictive Phase Separation Approach for Efficient Formation

TL;DR

This paper introduces a predictive, theory-based method for fabricating Janus polymersomes with high yield, enabling controlled design and functionalization for applications in drug delivery and synthetic cells.

Contribution

It presents a rational, Flory-Huggins theory-based approach to predict and experimentally validate the self-assembly of asymmetric Janus polymersomes, improving upon empirical methods.

Findings

Achieved over 90% yield of stable Janus giant unilamellar vesicles.

Developed a phase diagram linking mixing energy to vesicle morphology.

Demonstrated extrusion of vesicles while maintaining Janus morphology.

Abstract

Janus particles, with their intrinsic asymmetry, are attracting major interest in various applications, including emulsion stabilization, micro/nanomotors, imaging, and drug delivery. In this context, Janus polymersomes are particularly attractive for synthetic cell development and drug delivery systems. While they can be achieved by inducing a phase separation within their membrane, their fabrication method remains largely empirical. Here, we propose a rational approach, using Flory-Huggins theory, to predict the self-assembly of amphiphilic block copolymers into asymmetric Janus polymersomes. Our predictions are experimentally validated by forming highly stable Janus giant unilamellar vesicles (JGUVs) with a remarkable yield exceeding 90% obtained from electroformation of various biocompatible block copolymers. We also present a general phase diagram correlating mixing energy with polymersome morphology, offering a valuable tool for JGUV design. These polymersomes can be extruded to achieve quasi-monodisperse vesicles while maintaining their Janus-like morphology, paving the way for their asymmetric functionalization and use as active carriers.