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

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., ¹O₂). 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 ¹O₂ owing to site isolation of porphyrin ligands, enhanced intersystem crossing by heavy Hf centers, and facile ¹O₂ diffusion through porous DBP–UiO nanoplates. Consequently, DBP–UiO displayed greatly enhanced PDT efficacy both <i>in vitro</i> and <i>in vivo</i>, 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