Mixed-Ligand Metal–Organic Frameworks for All-in-One Theranostics with Controlled Drug Delivery and Enhanced Photodynamic Therapy

Mixed-ligand metal-organic frameworks (MOFs) multiply the properties and improve the versatility of conventional MOFs for theranostic applications. A tumor targeting and tumoral microenvironment-responsive system is significant for specific and efficient cancer theranostics. Herein, we report a kind of versatile mixed-porphyrin ligand MOF as a multifunctional matrix for multimodality-imaging-guided synergistic therapy. Tetrakis(4-carboxyphenyl)porphyrin (TCPP) shows the properties of fluorescence (FL) and photodynamic therapy (PDT), while Mn-TCPP owns magically the properties of T₁-weighted magnetic resonance (MR) imaging and photothermal conversion for photothermal imaging and photothermal therapy (PTT). Because of the same coordination capacity and mode of TCPP and Mn-TCPP to Zr⁴⁺ ions, MOFs with adjustable ligand ratios were easily prepared. The mixed-ligand MOFs exhibited a high drug loading capacity for 10-hydroxycamptothecin (HCPT, 65%). After modification with hyaluronic acid (HA) through a disulfide bond (-S-S-), the MOF-S-S-HA composites possess enhanced PDT and tumor-targeted redox-responsive drug release properties due to the -S-S- bond. Thus, excellent fluorescence, MR, and photothermal trimodality imaging, redox-responsive drug release, and enhanced PDT/PTT are integrated together in the mixed-ligand MOFs as "all-in-one" theranostic agents.