Mn-doped MOF nanoparticles mitigating hypoxia via in-situ substitution strategy for dual-imaging guided combination treatment of microwave dynamic therapy and chemotherapy.

Microwave dynamic therapy (MWDT) destroy tumor cells using reactive oxygen species (ROS), but its effectiveness is limited by low ROS production and intracellular oxygen (O) availability. This study presents a novel strategy using manganese (II) ion (Mn) doped iron (Fe)-based metal-organic framework (Fe MOF) nanoparticles (NPs) to enhance both O generation and ROS production for improved MWDT. Incorporating Mn into Fe MOF narrows the bandgap from 0.673 eV to 0.429 eV, improving the separation of electronic-hole pair and increasing ROS yield. Meanwhile, Mn-porphyrin nanocomplexes facilitate the decomposition of hydrogen peroxide to Oin situ. Additionally, encapsulating the chemotherapeutic drug gemcitabine (GEM) within NPs and surface-modifying with Pluronic F127 creates Mn-Fe MOF@GEM@F127 (MMGF) NPs, which are suitable for photoacoustic/magnetic resonance imaging guidance (relaxivity, r: 2.007 mMs). The microwave (MW)/pH dual responsive GEM release works synergistically with MWDT, thereby more effectively disrupting tumor cells. This strategy differs from monotherapy by using MW sensitizers to enhance O production, which not only increases the efficiency of ROS generation in MWDT but also makes subsequent chemotherapy more effective while reducing the side effects of conventional chemotherapy. This combined treatment reduced HONE-1 cell proliferation and tumor growth by 89.95 % and 96.12 %, respectively. The study proposes a versatile strategy to significantly improve both MWDT and chemotherapy efficacy with potential applications to various cancers.