Abstract

AbstractThe first attempt of constructing supramolecular prodrug micelles based on the host‐guest interaction between water‐soluble pillar[6]arene (WP6) and a novel doxorubicin (DOX)‐based drug‐drug conjugate (G) is reported, in which the drug‐drug conjugate is synthesized by conjugating anticancer drug DOX with another drug isoniazide via the acid‐cleavable hydrazone bond. The obtained WP6⊃G micelles are stable under physiological conditions, whereas the cumulative release of DOX is approximate to 100% within 30 min at pH 5.5 by simulating the endo‐lysosomal environment at 37°C. Therefore, this WP6‐based prodrug micelles can achieve efficient DOX accumulation in the acidic tumor cells within a short period of time, which is very important and valuable; meanwhile it can also reduce the unexpected premature burst release under physiological condition. Furthermore, cellular internalization and localization experiments demonstrated that these prodrug micelles enter cancer cells mainly via endocytosis and can lead to significant drug accumulation in SKOV3 cancer cells, implying its promising future for cancer therapy.

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