Nanoscale Two-Dimensional FeII- and CoII-Based Metal–Organic Frameworks of Porphyrin Ligand for the Photodynamic Therapy of Breast Cancer

Abstract

The delivery of biocompatible reagents into cancer cells can elicit an anticancer effect by taking advantage of the unique characteristics of the tumor microenvironment (TME). In this work, we report that nanoscale two-dimensional FeII- and CoII-based metal–organic frameworks (NMOFs) of porphyrin ligand meso-tetrakis (6-(hydroxymethyl) pyridin-3-yl) porphyrin (THPP) can catalyze the generation of hydroxyl radicals (•OH) and O2 in the presence of H2O2 that is overexpressed in the TME. Photodynamic therapy consumes the generated O2 to produce a singlet oxygen (1O2). Both •OH and 1O2 are reactive oxygen species (ROS) that inhibit cancer cell proliferation. The FeII- and CoII-based NMOFs were non-toxic in the dark but cytotoxic when irradiated with 660 nm light. This preliminary work points to the potential of porphyrin-based ligands of transition metals as anticancer drugs by synergizing different therapeutic modalities.

[FeIIICl(TMPPH2)][FeIIICl4]2: A Stand-Alone Molecular Nanomedicine That Induces High Cytotoxicity by Ferroptosis

“…In the ultraviolet–visible (UV-Vis) spectra ( Figure 1 d), the Soret band of the free H 2 TMPP at 419 nm underwent a significant blueshift to 398 nm upon the chelation of Fe 3+ . In addition, the Q bands coalesced into two, due to the change of symmetry from D 2h of H 2 TMPP to C 4v of Fe-TMPP [ 26 , 27 ]. Notably, an additional absorption band at around 650 nm also appeared, presumably due to the charge transfer between Fe 3+ and the ligand [ 28 ].…”

“…High valent transition metal ions Fe 3+ and Cu 2+ exhibit peroxidase-like activity to generate reactive •OH, by utilizing the overexpressed H 2 O 2 in the TME, thereby eliciting nonspecific damage inside cancer cells [ 6 , 7 , 8 , 26 ]. The TME also reduces Fe 3+ and Cu 2+ to Fe 2+ and Cu + through a reaction with the overexpressed GSH to initiate Fenton and Fenton-like reactions, which also generate •OH from H 2 O 2 .…”

[Fe^IIICl(TMPPH₂)][Fe^IIICl₄]₂: A Stand-Alone Molecular Nanomedicine that Induces High Cytotoxicity by Ferroptosis

“…In addition, the Q bands coalesced into two, due to the change of symmetry from D2h of H2TMPP to C4v of Fe-TMPP. [17,18] Notably, an additional absorption band at around 650 nm also appeared, presumably due to the charge transfer between Fe 3+ and the ligand. [19] Notably, the UV-Vis spectrum of Fe-TMPP exhibited an undulating baseline, indicating lighting scattering by nanoparticle formation in an aqueous solution.…”

“…High valent transition metal ions Fe 3+ and Cu 2+ exhibit peroxidase-like activity to generate reactive •OH by utilizing the overexpressed H2O2 in the TME, thereby eliciting nonspecific damage inside cancer cells. [6][7][8]17] The TME also reduces Fe 3+ and Cu 2+ to Fe 2+ and Cu + by reaction with the overexpressed GSH to initiate Fenton and Fenton-like reactions, which also generate •OH from H2O2. The peroxidase-like activity of the Fe 3+ -rich Fe-TMPP was therefore assayed using 3,3',5,5'tetramethylbenzidine (TMB).…”