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

TLDR

Photodynamic therapy (PDT) is an effective anticancer procedure that relies on tumor‑localized photosensitizers activated by light to produce cytotoxic reactive oxygen species such as singlet oxygen. The study reports the rational design of a hafnium‑porphyrin nanoscale metal‑organic framework, DBP‑UiO, as an exceptionally potent photosensitizer for treating resistant head and neck cancer. DBP‑UiO generates singlet oxygen efficiently through site‑isolated porphyrin ligands, enhanced intersystem crossing by heavy hafnium centers, and facile diffusion of singlet oxygen through its porous nanoplates. DBP‑UiO achieved markedly improved PDT efficacy in vitro and in vivo, eradicating tumors in 50 % of mice after a single dose and light exposure, and establishing NMOFs as a promising class of potent agents for treating resistant cancers.

Abstract

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.