Transformative Supramolecular Vesicles Based on Acid‐Degradable Acyclic Cucurbit[n]uril and a Prodrug for Promoted Tumoral‐Cell Uptake. Issue 9 (14th January 2019)

• Record Type: Journal Article
• Authors: Mao, Weipeng; Mao, Dake; Yang, Fan; Ma, Da
• Is Part Of: Chemistry. Volume 25:Issue 9(2019)
• Page Start: 2272
• Page End: 2280
• Publication Date: 2019-01-14
• Subjects: charge conversion -- drug delivery -- host–guest systems -- self-assembly -- supramolecular vesicles; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201804835
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Smart supramolecular vesicles constructed by host–guest interactions between "acid‐degradable" acyclic cucurbit[ n ]uril (CB[ n ]) and a doxorubicin prodrug are reported. "Acid‐degradable" acyclic CB[ n ] is a high‐affinity host for several common antitumor drugs, and its degradation leads to a more dramatic decrease in binding affinity than that observed for "acid‐sensitive" hosts. Supramolecular complexation between acid‐degradable acyclic CB[ n ] and a doxorubicin prodrug resulted in the formation of negatively charged supramolecular vesicles. The prodrug strategy allowed doxorubicin to be conjugated to vesicles in a stable manner with a high drug‐loading ratio of 20 %. The resulting supramolecular vesicles were responsive to tumor acidity (pH 6.5). Induced by mildly acidic conditions (pH 6.5–5.5), acid‐degradable acyclic CB[ n ] could be degraded, and this led to a vesicle‐to‐micelle transition to form positively charged micelles. This transition resulted in a pH‐dependent change in size and surface charge, which improved tumoral‐cell uptake for doxorubicin. Abstract : Improved uptake : Smart supramolecular vesicles were constructed by host–guest interactions between "acid‐degradable" acyclic cucurbit[ n ]uril (CB[ n ]) and a doxorubicin prodrug. Under mildly acidic conditions (pH 6.5–5.5), CB[ n ] degraded, which led to a vesicle‐to‐micelle transition. This transition resulted in a pH‐dependent change in size and surface charge, which improved the uptake of doxorubicin by tumor cells (see figure).