Cucurbit[8]uril-Based Giant Supramolecular Vesicles: Highly Stable, Versatile Carriers for Photoresponsive and Targeted Drug Delivery

Highly stable giant supramolecular vesicles were constructed by hierarchical self-assembly of cucurbit[8]uril (CB[8])-based supra-amphiphiles for photoresponsive and targeted intracellular drug delivery. These smart vesicles can encapsulate the model drugs with high loading efficiencies and then release them by manipulating photoswitchable CB[8] heteroternary complexation to regulate the formation and dissociation of supra-amphiphiles that cause dramatic morphological changes of the assemblies to achieve remote optically controlled drug delivery. More importantly, the confocal microscopy analysis, cellular uptake experiment, and cell viability assay have shown that the giant vesicles are able to maintain the structural integrity and stability within actual cellular environments and exhibit obvious advantages for intracellular drug delivery such as low toxicity, easy surface modification for tumor-targeting selectivity, and rapid internalization into different human cancer cell lines. A synergistic mechanism that integrates multiple pathways including energy-dependent endocytosis, macropinocytosis, cholesterol-dependent endocytosis, and microtubule-related endocytosis was determined to facilitate the internalization process. Moreover, cytotoxicity experiments and flow cytometric analysis have demonstrated that the doxorubicin hydrochloride-loaded vesicles exhibited a significant therapeutic effect for tumor cells upon UV light irradiation, which makes the photoresponsive system more promising for potential applications in pharmaceutically relevant fields.

通过基于葫芦[8]脲（CB[8]）的超两亲物的分层自组装构建了高度稳定的巨型超分子囊泡，用于光响应和靶向细胞内药物递送。这些智能囊泡可以高负载效率封装模型药物，然后通过操纵光开关CB[8]异三元络合来释放它们，以调节超两亲物的形成和解离，从而引起组件的剧烈形态变化，从而实现远程光控药物递送。更重要的是，共聚焦显微镜分析、细胞摄取实验和细胞活力测定表明，巨型囊泡能够在实际细胞环境中保持结构完整性和稳定性，并在细胞内药物递送方面表现出明显的优势，例如低毒性、易于肿瘤靶向选择性的表面修饰以及快速内化到不同的人类癌细胞系中。确定了整合多种途径的协同机制，包括能量依赖性内吞作用、巨胞饮作用、胆固醇依赖性内吞作用和微管相关内吞作用，以促进内化过程。此外，细胞毒性实验和流式细胞术分析表明，负载盐酸阿霉素的囊泡在紫外光照射下对肿瘤细胞表现出显着的治疗效果，这使得光响应系统在药物相关领域更具潜在应用前景。