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

Abstract

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 T 2-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.

Heterostructures Made of Upconversion Nanoparticles and Metal–Organic Frameworks for Biomedical Applications

“…Recently, Lin group designed and synthesized UCNP‐MOF Janus structures (UPFB) for synergistic tumor therapy including PDT, chemodynamic therapy (CDT), and sonodynamic therapy (SDT) ( Figure a). [ 108 ] In this work, ultrasound was selected as an exogenous energy source for activation of UPFB to heighten ROS generation, which made up for the inefficient PDT caused by low energy transfer in the heterodimers. Besides, Fe 3+ ions coordinated in porphyrin‐based PCN‐224(Fe) MOFs served as catalase‐like nanozymes, which not only catalyzed the decomposition of H 2 O 2 to O 2 to alleviate tumor hypoxia (Figure 12b), but also suppressed other pathways consuming generated ROS by intracellular GSH depletion.…”

“…Reproduced with permission. [ 108 ] Copyright 2021, American Chemical Society. e) Schematic illustration of the preparation and bactericidal activity of UCNP@PCN@LA‐PVDF nanocomposites.…”

Tumor-targeted biomimetic nanoplatform precisely integrates photodynamic therapy and autophagy inhibition for collaborative treatment of oral cancer

“…15 The high PS construction ratio, low self-quenching rate, efficient ROS diffusion, high drug loading rate and flexible modifiable sites make MOF photodynamic materials a highly promising multifunctional photodynamic nanotherapy platform. 16 However, relying solely on the photodynamic action of MOF PSs still has the disadvantages of poor curative effect, a tendency for recurrence and the need for repeated treatments for more malignant tumor types like oral cancer. Therefore, using a highly porous structure of MOFs to load drugs that have a synergistic effect with PDT will greatly improve the efficiency of combined therapy.…”

Multiple stimuli-responsive nanosystem for potent, ROS-amplifying, chemo-sonodynamic antitumor therapy

“…The common feature of all these strategies is that oxygen plays an essential role during the treatment processes. To further amplify the generation of ROS, extensive research has been aimed at designing O 2 -independent ROS production system to overcome hypoxia induced SDT resistance [ [24] , [25] , [26] , [27] , [28] ]. For instance, Zhang applied a Ti-TCPP MOF platform to generate ROS in a hypoxic environment and facilitate oxygen-independent SDT treatment [ 29 ].…”