Engineered MOF-Enzyme Nanocomposites for Tumor Microenvironment-Activated Photodynamic Therapy with Self-Luminescence and Oxygen Self-Supply

Photodynamic therapy (PDT) is a promising strategy forcancer treatment.However, its efficiency is hindered by three key parameters, namely,limited penetration depth of external light, tumor hypoxia, and self-aggregationof photosensitizers. Herein, we fabricated a novel all-in-onechemiluminescence-PDT nanosystem through the integration of an oxygen-supplyingprotein (hemoglobin, Hb) and a luminescent donor (luminol, Lum) inhierarchically engineered mesoporous porphyrinic metal-organicframework (MOF) nanoparticles. Mechanistically, the in situ chemiluminescenceof Lum is activated by the high concentration of H2O2 in 4T1 cancer cells and further catalyzed by Hb and thenabsorbed by the porphyrin ligands in MOF nanoparticles through chemiluminescenceresonance energy transfer. The excited porphyrins then sensitize oxygensupplied by Hb to produce sufficient reactive oxygen species thatkill cancer cells. The MOF-based nanocomposite demonstrates excellentanticancer activity both in vitro and in vivo, with eventually a 68.1%tumor inhibition rate after intravenous injections without externallight irradiation. This self-illuminating, oxygen-self-supplying nanosystemintegrates all essential components of PDT into one simple nanoplatform,demonstrating great potential for the selective phototherapy of deep-seatedcancer.

Automated summary

This study developed a novel chemiluminescence-photodynamic therapy (PDT) nanosystem by integrating an oxygen-supplying protein (hemoglobin, Hb) and a luminescent donor (luminol, Lum) into hierarchically engineered mesoporous porphyrinic metal-organic framework (MOF) nanoparticles. The system activated luminescence through chemiluminescence resonance energy transfer and produced reactive oxygen species for cancer cell killing, resulting in an excellent anticancer activity both in vitro and in vivo. This self-illuminating, oxygen-self-supplying nanosystem integrates essential components of PDT and holds great potential for selective phototherapy of deep-seated cancer.