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

Abstract

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.

Cucurbit[8]uril (CB[8])‐Based Supramolecular Switches

“…[68] Angewandte Chemie Minireviews drug delivery vehicle.I nf act, this strategy has been recently exploited for the targeted photo-controlled delivery of doxorubicin from supramolecular vesicles. [69] Other examples of the light-driven Ty pe E-C interconversion have been reported, showing the versatility of the approach for the light-controlled self-assembly of new functional materials,i ncluding hybrid raspberry-like colloids, [70] supramolecular polymeric nanoparticles [71] or polymeric networks. [72] Furthermore,i nar ecent study,J onkheijm and coworkers have used the Ty pe E-C photoswitch for the reversible immobilization of cowpea chlorotic mottle virus nanocages on surfaces (Scheme 19).…”

Dynamic supramolecular polymers built from cucurbit[n]urils and viologens

“…Such vesicles have been successfully employed to encapsulate fibroblast growth factor, extending its bioactivity without the necessity of excipients such as heparin . Hetero‐ternary complexes involving the host–guest CB[8]‐maleimide‐modified MV and azo‐dyes have been self‐assembled on the surface of giant vesicles to be used as models of optically active drug carriers for delivery to specific targets . On the other hand, Das and co‐workers have established that different aromatic amino acids can form vesicles through ternary complexes with CB[8] and an amphiphilic viologen.…”

Self‐Assembly of Spherical Organic Molecules to Form Hollow Vesicular Structures in Water for Encapsulation of an Anticancer Drug and Its Release

“…The data revealed that vesicle(C 3 ) was found to be the most efficient in loading DOX (10.5 %) (Figure ). Since all the vesicles reported herein were found to be stable up to pH 3 (Figure S8, supporting information), we explored a well‐known vesicle destroyer (Triton X‐100) in order to deliver the encapsulated drug in a stimuli responsive fashion. DLS data of all the vesicles in presence of Triton X‐100 (5 μL) showed significantly smaller particle size (≈10 nm) indicating disruption of the vesicular structures (Figure S9, supporting information).…”