Dimensional Reduction Enhances Photodynamic Therapy of Metal-Organic Nanophotosensitizers.

ABSTRACT

Herein we report that dimensional reduction from three-dimensional nanoscale metal-organic frameworks (nMOFs) to two-dimensional nanoscale metal-organic layers (nMOLs) increases the frequency of encounters between photosensitizers and oxygen and facilitates the diffusion of singlet oxygen from the nMOL to significantly enhance photodynamic therapy. The nMOFs and nMOLs share the same M12-oxo (M = Zr, Hf) secondary building units and 5,15-di-p-benzoatoporphyrin (DBP) ligands but exhibit three-dimensional and two-dimensional topologies, respectively. Molecular dynamics simulations and experimental studies revealed that the nMOLs with a monolayer morphology enhanced the generation of reactive oxygen species and exhibited over an order of magnitude higher cytotoxicity over the nMOFs. In a mouse model of triple-negative breast cancer, Hf-DBP nMOL showed 49.1% more tumor inhibition, an 80% higher cure rate, and 16.3-fold lower metastasis potential than Hf-DBP nMOF.