Polymersomes with inhomogeneous membranes, asymmetrical coronas and fused membranes and coronas

Abstract

Polymersomes (also known as polymer vesicles) are hollow nanoparticles (comprising a lumen, a membrane and inner and outer coronas) which are considered as promising candidates for biomedical applications such as controlled drug release, gene delivery, cell mimicking, highly efficient antibacterial treatment and cancer theranostics. Conventional synthetic polymersomes are composed of a dense homogeneous membrane, identical inner and outer coronas and spatially-separated functional substructures. In comparison to bio-membranes (or cellular membranes), the characteristics of synthetic membranes are often insufficient to meet the requirements for biomedical applications, making such polymersomes inefficient or even incapable for such duties. It is still a challenge for synthetic polymersomes to achieve efficient trans-membrane trafficking of macromolecules, different functionalization between inner and outer coronas, or efficient synergy of functions between their coronas and membranes. The lack of these characteristics therefore inhibits gene delivery, theranostic applications and antibacterial properties. To investigate and ultimately improve the above-mentioned properties of polymersomes, we focus on three different types of polymersome structures: (1) Polymersomes with inhomogeneous membranes, where the membrane is composed of different micro-phases with various functions; (2) polymersomes with asymmetrical coronas, whose inner coronas differ from outer coronas in chemical composition, or have different modifications; (3) polymersomes with fused membranes and coronas, where the membrane and coronas become fused and thus function together. These three polymersomes allow specific biomedical applications and provide new design strategies for their clinical applications. Herein, we review the related research which assesses the membrane structures and preparation strategies of the above polymersomes. Finally, we summarize the design principles and possible biomedical applications of the polymersomes with the various structures. For polymersomes with inhomogeneous membranes: The membrane structure is mainly attributed to micro-phase separation, and cross-linking can be used to initiate the micro-phase separation process. This is because of the high chain flexibility of the polymer which results into a modularly functionalized polymersome membrane. For polymersomes with asymmetrical coronas: The structure mainly results from the different block volumes between the inner and outer coronas (located within the lumen and surface of the polymersome, respectively). The hydrophilic block with a lower volume faces the lumen, while the block with a larger volume is located on the outer surface of the polymersome. For polymersomes with fused membranes and coronas: The polymer, with various architectures (such as alternating polymer, statistical polymer or even homopolymer), congregates the membrane-forming and corona-forming polymer segments. This leads to an enhanced synergy during clinical applications. In summary, the design of polymersome structures involves different aspects from both polymer and phase structures. Biomedical practices or clinical translations require materials which are biocompatible, controlled-biodegradable, available by mass production, etc. Future polymersomes will be more suitable for clinical practices, and are therefore promising for biomedical applications.