Metal–Organic Framework-Based Nanoagents for Effective Tumor Therapy by Dual Dynamics-Amplified Oxidative Stress

Abstract

Overproduction of reactive oxygen species (ROS) within tumors can cause oxidative stress on tumor cells to induce death, which has motivated us to develop ROS-mediated tumor therapies, such as typical photodynamic therapy (PDT) and Fenton reaction-mediated chemodynamic therapy (CDT). However, these therapeutic modalities suffer from compromised treatment efficacy owing to their limited generation of highly reactive ROS in a tumor microenvironment (TME). In this work, a nanoscale iron-based metal–organic framework, MIL-101­(Fe), is synthesized as a Fenton nanocatalyst to perform the catalytic conversion of hydroxyl radicals (·OH) from hydrogen peroxide (H2O2) under the acidic environment and as a biocompatible and biodegradable nanocarrier to deliver a 5,10,15,20-tetrakis­(4-carboxyphenyl)­porphyrin (TCPP) photosensitizer for light-activated singlet oxygen (1O2) generation. By coupling such chemodynamic/photodynamic effects, the photosensitizer-integrated nanoagents (MIL-101­(Fe)@TCPP) could enable more ROS production within tumors to induce amplified oxidative damage for tumor-specific synergistic therapy. In vitro results show that MIL-101­(Fe)@TCPP nanoagents achieve the acid-responsive CDT and effective PDT, and synergistic CDT/PDT provides an enhanced therapeutic effect. Ultimately, based on such synergistic therapy, MIL-101­(Fe)@TCPP nanoagents cause a significant tumor growth inhibition in vivo without severe side effects, showing great potential for anti-tumor application.

Progress of Nanomaterials in Photodynamic Therapy Against Tumor

“…The macrophages that promote tumor growth are M2 phenotype and have the function of repairing injury and inhibiting inflammatory response in normal tissues. The macrophages that inhibit tumor growth are M1 phenotype, which can induce inflammatory response and activate immune response to kill tumor cells ( Chen J. et al, 2021 ). In the process of tumorigenesis, TAMs can often stimulate angiogenesis, promote tumor cell migration and invasion, and mediate tumor immune escape ( De Lerma et al, 2021 ).…”

“…The nucleus is the control center of cellular biological activities, and targeting PDT to the nucleus can lead to severe DNA damage and inactivation of nuclear enzymes ( Teng et al, 2021 ). Base on this, Chen and his team proposed a PDT strategy of “one treatment, multiple irradiation” Chen X. et al (2021) . They modified hollow mesoporous silica nanoparticles with amine group with acidification effect and loaded RB and UCNPs to synthesize UCNP/RB@mSiO 2 -NH based on the lysosome-nucleus pathway.…”

“…Chen et al’s research focused on designing nanocarriers for the transport of Fenton catalysts or metal ions such as iron ions. They synthesized MIL-101(Fe)@TCPP using nanoscale iron-based metal-organic framework MIL-101(Fe) loaded with 5,10,15,20-tetrakis (4-carboxyphenyl) porphyrin (TCPP) PS Chen et al (2021d) . MIL-101(Fe) catalyzed the conversion of H 2 O 2 to OH through Fenton reaction under acidic TME, and served as a nanocarrier to deliver TCPP PS to generate photoactivated 1 O 2 for tumor-specific therapy without serious side effects, showing antitumor great potential for applications.…”

Antibacterial Cascade Catalytic Glutathione-Depleting MOF Nanoreactors

“…MIL with PODlike activity acted as carriers. 51 MnFe 2 O 4 @MIL/Au catalyzed H 2 O 2 to generate a large amount of ROS to kill bacteria (Figure 1b). Note that bacteria leak GSH when destroyed by ROS.…”

Interface-Engineered Mesoporous FeB with Programmed Drug Release for Synergistic Cancer Theranostics

“…Among them, iron-based nanostructures stand out because the exogenous administration of an essential element would avoid the potential adverse effects to human health. To date, tremendous efforts have been devoted to developing Fe-based oxides, , sulfides, , carbides, − nitrides, − and Fe-based MOFs, − where the Fe-based MOF with a mesoporous structure witnesses obvious renown due to its inherent advantage in carrying chemotherapeutic drugs as well as multi-therapeutic modes. Of note, the facile synthesis of mesoporous Fe-based sulfides, carbides, and nitrides to be developed as nanoagents has long been a challenge.…”