Fusiform-Like Copper(II)-Based Metal–Organic Framework through Relief Hypoxia and GSH-Depletion Co-Enhanced Starvation and Chemodynamic Synergetic Cancer Therapy

Abstract

The therapeutic effect of traditional chemodynamic therapy (CDT) agents is severely restricted by their weakly acidic pH and glutathione (GSH) overexpression in the tumor microenvironment. Here, fusiform-like copper­(II)-based tetrakis­(4-carboxy phenyl)­porphyrin (TCPP) nanoscale metal–organic frameworks (nMOFs) were designed and constructed for the first time (named PCN-224­(Cu)-GOD@MnO2). The coated MnO2 layer can not only avoid conjugation of glucose oxidase (GOD) to damage normal cells but also catalyzes the generation of O2 from H2O2 to enhance the oxidation of glucose (Glu) by GOD, which also provides abundant H2O2 for the subsequent Cu+-based Fenton-like reaction. Meanwhile, the Cu2+ chelated to the TCPP ligand is converted to Cu+ by the excess GSH in the tumor, which reduces the tumor antioxidant activity to improve the CDT effect. Next, the Cu+ reacts with the plentiful H2O2 by enzyme catalysis to produce a toxic hydroxyl radical (•OH), and singlet oxygen (1O2) is synchronously generated from combination with Cu+, O2, and H2O via the Russell mechanism. Furthermore, the nanoplatform can be used for both TCPP-based in vivo fluorescence imaging and Mn2+-induced T 1-weighted magnetic resonance imaging. In conclusion, fusiform-like PCN-224­(Cu)-GOD@MnO2 nMOFs facilitate the therapeutic efficiency of chemodynamic and starvation therapy via combination with relief hypoxia and GSH depletion after acting as an accurate imaging guide.

Recent Advances in Nanomaterial‐Based Nanoplatforms for Chemodynamic Cancer Therapy

“…Based on this, a fusiform-like nanoscale MOF (nMOF, named PCN-224(Cu)-GOx@MnO 2 ) was reported by Yang et al (Figure 4a). [57] The nMOF is composed of Cu 2+ , tetrakis(4-carboxy phenyl)porphyrin (TCPP) ligands, and GOx and MnO 2 coated. In their structure design, the coated MnO 2 layer acts as a gatekeeper to avoid the conjugated GOx to damage normal cells and as a nanozyme to catalyze the generation of O 2 from H 2 O 2 to promote the oxidation of Glu by GOx.…”

“…Recently, Zhang et al reported the black Reproduced with permission. [57] Copyright 2008, American Chemical Society. b) Schematic illustration of the design of FeCysPW@ZIF-82@CAT Dz.…”

Photoactivatable nanogenerators of reactive species for cancer therapy

“…ROS can destroy tumor cells through multifactorial mechanisms, including oxidizing the biological macromolecules, destroying angiogenesis to cut off the supply of nutrients to tumor cells [ 36 , 37 ]. Typically, five therapeutic strategies including radiation therapy [ [38] , [39] , [40] , [41] ], chemodynamic therapy [ [42] , [43] , [44] , [45] , [46] ], sonodynamic therapy [ [47] , [48] , [49] , [50] ], bioreductive chemotherapeutics (e.g., tirapazamine, TPZ) [ [51] , [52] , [53] , [54] ], and photodynamic therapy (PDT) [ [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] ] can generate ROS. Among all these approaches, PDT-based cancer therapies have been extensively exploited.…”

Energy‐converting biomaterials for cancer therapy: Category, efficiency, and biosafety

“…Cu‐based chemical‐driven ROS‐ECBs, such as Cu 2+ ‐doped biomaterials (Li et al, 2019; Liu et al, 2019a; Wang et al, 2019), copper sulfide (Pan et al, 2020; Wang et al, 2020), and Cu 2‐ x Se (Wang, Guo, et al, 2020), exhibited excellent performance in CDT compared with Fe‐based chemical‐driven ROS‐ECBs. It has been reported that the Cu + ‐catalyzed Fenton‐like reaction with the high reaction rate could occur in a wider range of pH compared with Fe 2+ (Wang et al, 2020).…”