Department of Chemistry, University of Warwick, Coventry CV4 7AL, U.K.
Eindhoven University of Technology, P.O. Box 513, Eindhoven 5600MB, The Netherlands.
Biomacromolecules. 2024 Sep 9;25(9):6050-6059. doi: 10.1021/acs.biomac.4c00726. Epub 2024 Aug 15.
The design of biocompatible and biodegradable nanostructures with controlled morphological features remains a predominant challenge in medical research. Stimuli-responsive vesicles offer significant advantages in drug delivery, biomedical applications, and diagnostic techniques. The combination of poly(2-oxazoline)s with biodegradable polymers could provide exceptional biocompatibility properties and be proposed as a versatile platform for the development of new medicines. Therefore, poly(2-ethyl-2-oxazoline) (PEtOx) and poly(2-isopropyl-2-oxazoline) (PPrOx) possessing a hydroxy terminal group that acts as an initiator for the ring-opening polymerization of d,l-lactide (DLLA) have been utilized in this study. The resulting amphiphilic block polymers were used to create polymersomes, which undergo solvent-dependent reorganization into bowl-shaped vesicles or stomatocytes. By blending PEtOx--PDLLA and PPrOx--PDLLA copolymers, a thermoresponsive stomatocyte was generated, where the opening narrowed and irreversibly closed with a slight increase in the temperature. Detailed transmission electron microscopy analysis reveals the formation of both closed and fused stomatocytes upon heating the sample above the critical solution temperature of PPrOx.
具有可控形态特征的生物相容性和可生物降解纳米结构的设计仍然是医学研究中的主要挑战。刺激响应囊泡在药物输送、生物医学应用和诊断技术方面具有显著优势。聚(2-恶唑啉)与可生物降解聚合物的结合可以提供卓越的生物相容性,并被提议作为开发新药的通用平台。因此,本研究中使用了具有羟基端基的聚(2-乙基-2-恶唑啉)(PEtOx)和聚(2-异丙基-2-恶唑啉)(PPrOx),其可以作为 d,l-丙交酯(DLLA)开环聚合的引发剂。所得两亲嵌段聚合物用于制备聚合物囊泡,其在溶剂依赖性作用下重组为碗状囊泡或口形细胞。通过混合 PEtOx-PDLLA 和 PPrOx-PDLLA 共聚物,生成了热敏性口形细胞,其中随着温度的轻微升高,开口变窄并不可逆地关闭。详细的透射电子显微镜分析表明,在将样品加热到 PPrOx 的临界溶液温度以上时,会形成闭合和融合的口形细胞。