Although nanomedicines can passively target tumor through the enhanced permeability and retention (EPR) effect, their distribution and retention are limited by complex tumor microenvironment. Herein, a self-delivery supramolecular nanoplatform with shape-transforming capacity (Ce6-CD/ Fc-pep-PEG) is constructed by the host-guest interaction between chlorin e6-conjugated β-cyclodextrin (Ce6-CD) and ferrocene-modified FFVLG 3 C-PEG conjugates (Fc-pep-PEG). Following passive accumulation mediated by the EPR effect, hydrophobic Fc is oxidized to water-soluble Fc + by endogenous ROS in tumor sites. The resulting Fc + -pep-PEG fragment dissociated from Ce6-CD and recombined to nanofibers through the intermolecular hydrogen bonds among FFVLG 3 C peptide chains, thus enhancing the retention. Meanwhile, the Ce6-CD fragment still maintained the form of spherical micelles with a relatively smaller size to penetrate into the deep tumor regions. Moreover, the cascade Fenton reaction catalyzed by Fc generated •OH and O 2 to relieve hypoxia and amplify PDT efficiency. In turn, ROS generated by PDT promoted shape-transformation and continuous occurrence of Fenton reaction. In vitro and in vivo evaluations verify that through the positive feedback loop, Ce6-CD/ Fc-pep-PEG can induce a potent antitumor immune response and achieve ROS-potentiated elimination of primary tumor and bone metastasis.

12The latest and fastest-growing innovation in the medical field has been the advent of three-

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