Cyclodextrin-Activated Porphyrin Photosensitization for Boosting Self-Cleavable Drug Release

Supramolecular prodrugs that combine
the merits of stimuli-responsiveness
and targeting ability in a controllable manner have shown appealing
prospects in disease diagnostics and therapeutics. Herein, we report
that a new theranostic agent with the host–guest-binding-activated
photosensitization has been fabricated by a binary supramolecular
assembly consisting of the permethyl-β-cyclodextrin-grafted
hyaluronic acid and a combretastatin A-4-appended porphyrin derivative.
Illuminated by a red-light source, the production efficiency of singlet
oxygen (1O2) pronouncedly increases by ∼60-fold
once the porphyrin core is encapsulated by cyclodextrins. Consequently,
the cell-selective fluorescence emission is dramatically enhanced,
the microtubule-targeted drug is rapidly and completely released,
and the 1O2-involved combinational treatment
is simultaneously achieved both in vitro and in vivo. To be envisaged,
this complexation-boosted light-activatable photosensitizing prodrug
delivery system with improved photophysical performance and remarkable
phototheranostic outcomes will make a significant contribution to
the creation of more advanced stimulus-based biomaterials.