非均相膜、非对称冠及膜冠融合高分子囊泡

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

高分子囊泡是通过自组装构筑的具有"空腔-内冠-膜层-外冠"结构的纳米材料,在药物控释、基因递送、细胞仿生、抗菌和癌症诊疗等领域具有重要的应用前景.然而,传统高分子囊泡具有对称的内外冠结构、均一且致密的疏水膜,以及相对离散的膜冠功能分区,不能充分发挥囊泡的结构优势,进而难以应对生物医用过程中所面临的种种挑战,如基因治疗中大分子的跨膜运输,癌症诊疗中对内冠诊断、外冠靶向的差异化要求,细菌感染治疗中对膜冠协同、高效抗菌的需求等.因此,我们提出并设计了非均相膜囊泡、非对称冠囊泡、膜冠融合囊泡,针对性地解决了以上3个难题,为设计、合成新结构高分子囊泡,并推动其转化应用提供了新思路.本文总结了以上3种新结构囊泡的研究进展,并提出了设计生物医用高分子囊泡的原则.

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 transmembrane 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.