Exploiting Single Atom Iron Centers in a Porphyrin-like MOF for Efficient Cancer Phototherapy

In recent years, single-atom catalysts (SACs) have attracted enormous attention due their effectiveness in promoting a variety of catalytic reactions. However, the ability of SACs to enhance cancer phototherapies has received little attention to date. Herein, we synthesized a metal organic framework (MOF) rich in porphyrin-like single atom Fe(III) centers (denoted herein as porphyrin-MOF or P-MOF) and then evaluated the performance of the P-MOF for cancer treatment by photodynamic therapy (PDT) and photothermal therapy (PTT) under NIR (808 nm) irradiation, as well as photoacoustic imaging (PAI) of tumors. On acccount of the abundance of single atom Fe(III) centers, the P-MOF material demonstrated excellent performance for modulation of the hypoxic tumor microenvironment of Hela cell tumors in mice, while also demonstrating good properties as a photoacoustic imaging (PAI) agent. Density functional theory (DFT) calculations were used to elucidate the superior performance of P-MOF in these applications relative to Fe₂O₃ (a Fe(III) reference compound). The calculations revealed that the narrow band gap energy of P-MOF (1.31 eV) enabled strong absorption of NIR photons, thereby inducing nonradiative transitions that converted incident light into heat to promote PTT. Further, a facile change of the spin state of the single atom Fe(III) centers in P-MOF under NIR irradiation transformed coordinated triplet oxygen (³O₂) to singlet oxygen (¹O₂), benefiting PDT. This work demonstrates the great future potential of both SACs and MOFs as multifunctional agents for cancer treatment and tumor imaging.