Supramolecular Dual Polypeptides Induced Tubulin Aggregation for Synergistic Cancer Theranostics

• Published in: Journal of medicinal chemistry Vol. 65; no. 19; pp. 13473 - 13481
• Main Authors: Tang, Mian, Liu, Yao-Hua, Liu, Hua, Mao, Qiyue, Yu, Qilin, Kitagishi, Hiroaki, Zhang, Ying-Ming, Xiao, Lehui, Liu, Yu
• Format: Journal Article
• Language: English
• Published: American Chemical Society 13.10.2022
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/acs.jmedchem.2c01398

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.