Host–guest binding of tetracationic cyclophanes to photodynamic agents inhibits posttreatment phototoxicity and maintains antitumour efficacyElectronic supplementary information (ESI) available: Materials, methods, experimental details and additional spectra and images. CCDC 2194641, 2194643and 2194648. For ESI and crystallographic data in CIF or other electronic format see DOI: https://doi.org/10.1039/d2md00463a

In the past two decades, photodynamic therapy (PDT) has become an effective method for the treatment of cancer. However, the posttreatment residue of photodynamic agents (PDAs) causes long-term skin phototoxicity. Here, we apply naphthalene-derived, box-like tetracationic cyclophanes, named NpBoxes, to bind to clinically used porphyrin-based PDAs to alleviate their posttreatment phototoxicity by reducing their free content in skin tissues and 1O2quantum yield. We show that one of the cyclophanes, 2,6-NpBox, could include the PDAs to efficiently suppress their photosensitivity for the generation of reactive oxygen species. A tumour-bearing mouse model study revealed that, when Photofrin, the most widely used PDA in clinic, was administrated at a dose corresponding to the clinical one, 2,6-NpBox of the same dose could significantly suppress its posttreatment phototoxicity on the skin induced by simulated sunlight irradiation, without imposing a negative influence on its PDT efficacy.