Multifunctional DNAzyme-Anchored Metal–Organic Framework for Efficient Suppression of Tumor Metastasis

Abstract

High mortality and rapid development of metastasis requires the development of more effective antimetastasis strategies. However, conventional therapeutic methods, including surgery, radiation therapy, and chemotherapy, show less effectiveness in curbing the metastatic spread of cancer cells and the formation of metastases. A therapeutic platform, targeting the early stage of metastasis cascade, could effectively prevent metastasis dissemination. Herein, Fe/Mn-based metal–organic frameworks (FMM) were constructed for the delivery of a specific DNAzyme with high catalytic cleavage activity on the metastasis-involved Twist mRNA, thus efficiently inhibiting the invasion of cancer cells through DNAzyme-catalyzed gene silencing. Highly potent combined gene/chemodynamic therapy is achieved from the self-supplied DNAzyme cofactors and efficient glutathione depletion. Importantly, by virtue of the intrinsic photo-to-thermal conversion of the FMM nanocarriers, our combined therapeutic strategy could be further promoted under photothermal stimuli to speed up the Fenton reaction and to accelerate the release of the Twist DNAzyme with efficient gene therapy. Consequently, the effective elimination of tumors and the blockage of metastasis are simultaneously achieved under photothermal/magnetic resonance imaging guidance. This work aims at developing versatile theranostic agents to combat metastatic tumors.

A dual gate-controlled intelligent nanoreactor enables collaborative precise treatment for cancer nanotherapy

“…2a, the strongest absorbance intensity was acquired when exposed to an 808 nm laser, indicating the strong synergy between PTT and CDT. 42 These results were consistent with the depth of blue in the inset of Fig. 2a.…”

Metal‐Organic Frameworks Nanocarriers for Functional Nucleic Acid Delivery in Biomedical Applications

“…Copyright (2022), with permission from Publisher. (B) Applications of DNAzyme‐anchored nanoplatforms to inhibit tumor growth and metastasis [47] . Copyright (2022), with permission from Publisher.…”

Stimuli‐Responsive RNA‐Cleaving DNAzyme for Biomedical Application

“…Except for detection application, DNAzymes display great potential in gene silencing therapy due to their specific cleavage capability, flexible programmability, and relative stability in physiological environment [85–88] . Wang et al.…”

“…Except for detection application, DNAzymes display great potential in gene silencing therapy due to their specific cleavage capability, flexible programmability, and relative stability in physiological environment. [85][86][87][88] Wang et al em- bedded a DNAzyme targeting human early growth response-1 (EGR-1) in Cu/Zn bimetallic metal-organic framework (MOF) nanoparticles to construct a multifunctional nanoplatform for chemotherapy and gene therapy. [59] As shown in Figure 19A, after the nanoparticles enter cancer cells, the pH-responsive nanocarrier degrades to provide DNAzyme with cofactor Zn 2 + for tumor metastasis inhibition by cutting oncogene RNA substrates.…”