A biotin-functionalized calix[4]arene nanocarrier with intrinsic antitumor activity for combined chemo-photodynamic therapy.

Abstract

Conventional nanoplatforms often suffer from complicated fabrication, poor structural controllability, insufficient tumor targeting, and unsatisfied therapeutic efficacy. To address these issues, herein we rationally design and construct a novel calix[4]arene derivate CMP, whose upper rim is functionalized with pH-responsive biotin-PEG hydrophilic chains, and lower rim is dually modified with hydrophobic alkyl chains and antitumor pharmacophores. This "all-in-one" supramolecule can not only serve as an excellent supramolecular chemotherapeutic agent itself, but also act as a versatile carrier to co-deliver doxorubicin (DOX) and chlorin e6 (Ce6). The nanoplatform therefore integrates two types of chemotherapeutic modalities and biotin-targeted photodynamic therapy for multi-modal tumor treatment. Notably, in vivo experiments demonstrate that the resultant DOX@CMP@Ce6 nanosystem achieves a 90.5% tumor growth inhibition rate, while displaying biotin-mediated tumor tropism, excellent biocompatibility, and robust triple-modality combinatorial therapeutic effects. Collectively, this work provides key insights into the rational construction of multifunctional supramolecular platforms, reinforcing the broad prospects of calixarene derivatives for nanomedical applications.