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 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.