Supramolecular Dual Polypeptides Induced Tubulin Aggregation for Synergistic Cancer Theranostics

The
advent of macrocycle-based supramolecular chemistry
can offer
powerful strategies for regulating vital bioactivities in living systems
and bring about emerging technology in biomedical science. Herein,
we construct a supra-biomacromolecular nanosystem involving microtubules,
cell-permeable porphyrins, and antimitotic peptide-decorated permethyl-β-cyclodextrins
for promoting cell apoptosis in a cooperative manner. Through specific
polypeptide–tubulin recognition, cyclodextrin moieties are
capable of anchoring to the tubulin surface and providing abundant
hydrophobic microenvironments to accommodate the photosensitive porphyrins.
Consequently, spherical tubulin aggregates are formed, and reactive
oxygen species can be efficiently generated via the host–guest
complexation. The combined usage of complexation-promoted photodynamic
efficacy and tubulin aggregation gives more serious cell apoptosis
under light irradiation in vitro and in vivo. To be envisioned, this
supramolecularly enhanced photodynamic performance together with controlled
aggregation of natural biomacromolecules may be developed as an innovative
approach to improve the therapeutic potency against many diseases.