Nanoscale Metal–Organic Framework for Highly Effective Photodynamic Therapy of Resistant Head and Neck Cancer

[Image: see text] Photodynamic therapy (PDT) is an effective anticancer procedure that relies on tumor localization of a photosensitizer followed by light activation to generate cytotoxic reactive oxygen species (e.g., (1)O(2)). Here we report the rational design of a Hf–porphyrin nanoscale metal–organic framework, DBP–UiO, as an exceptionally effective photosensitizer for PDT of resistant head and neck cancer. DBP–UiO efficiently generates (1)O(2) owing to site isolation of porphyrin ligands, enhanced intersystem crossing by heavy Hf centers, and facile (1)O(2) diffusion through porous DBP–UiO nanoplates. Consequently, DBP–UiO displayed greatly enhanced PDT efficacy both in vitro and in vivo, leading to complete tumor eradication in half of the mice receiving a single DBP–UiO dose and a single light exposure. NMOFs thus represent a new class of highly potent PDT agents and hold great promise in treating resistant cancers in the clinic.