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Transformative Supramolecular Vesicles Based on Acid‐Degradable Acyclic Cucurbit[ n ]uril and a Prodrug for Promoted Tumoral‐Cell Uptake
Author(s) -
Mao Weipeng,
Mao Dake,
Yang Fan,
Ma Da
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201804835
Subject(s) - prodrug , vesicle , micelle , supramolecular chemistry , chemistry , doxorubicin , stereochemistry , combinatorial chemistry , organic chemistry , biochemistry , aqueous solution , membrane , biology , molecule , chemotherapy , genetics
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.