Upconverted Metal–Organic Framework Janus Architecture for Near-Infrared and Ultrasound Co-Enhanced High Performance Tumor Therapy

Strict conditions such as hypoxia, overexpression of glutathione (GSH), and high concentration of hydrogen peroxide (H₂O₂) in the tumor microenvironment (TME) limit the therapeutic effects of reactive oxygen species (ROS) for photodynamic therapy (PDT), chemodynamic therapy (CDT), and sonodynamic therapy (SDT). Here we fabricated a biocatalytic Janus nanocomposite (denoted as UPFB) for ultrasound (US) driven SDT and 808 nm near-infrared (NIR) light mediated PDT by combining core-shell-shell upconversion nanoparticles (UCNPs, NaYF₄:20%Yb,1%Tm@NaYF₄:10%Yb@NaNdF₄) and a ferric zirconium porphyrin metal organic framework [PCN-224(Fe)]. Our design not only substantially overcomes the inefficient PDT effect arising from the inadequate Förster resonance energy transfer (FRET) process from UCNPs (donor) to MOFs (acceptor) with only NIR laser irradiation, but also promotes the ROS generation via GSH depletion and oxygen supply contributed by Fe³⁺ ions coordinated in UPFB as a catalase-like nanozyme. Additionally, the converted Fe²⁺ from the foregoing process can achieve CDT performance under acidic conditions, such as lysosomes. Meanwhile, UPFB linked with biotin exhibits a good targeting ability to rapidly accumulate in the tumor region, verified by fluorescence imaging and T₂-weighted magnetic resonance imaging (MRI). In a word, it is believed that the synthesis and antitumor detection of UPFB heterostructures render them suitable for application in cancer therapeutics.