Danna Sun, Yuwei Song, Wenyan Gao, Boyang Lin, Bei Wang, Xinjian Yang, Shaochun Li, Yi Jin, Jinchao Zhang
{"title":"用于增强化学动力疗法和基因疗法以抑制肿瘤复发和转移的 DNA 模板纳米片。","authors":"Danna Sun, Yuwei Song, Wenyan Gao, Boyang Lin, Bei Wang, Xinjian Yang, Shaochun Li, Yi Jin, Jinchao Zhang","doi":"10.1016/j.ijpharm.2024.124910","DOIUrl":null,"url":null,"abstract":"<p><p>Recurrence and metastasis stand as the primary contributors to mortality among patients with triple-negative breast cancer post-surgery, presenting a formidable clinical obstacle. Chemodynamic therapy (CDT), leveraging metal-ion-mediated Fenton-like reactions within the tumor microenvironment (TME), emerges as a promising avenue for addressing cancer metastasis. Despite recent progress, challenges such as tumor cell antioxidant defenses and epithelial-mesenchymal transition (EMT) impede the efficacy of CDT. Here, we introduce a novel approach using DNA-templated nanosheets (Dz-MnO<sub>2</sub>) that combine the functions of Mn<sup>2+</sup>-mediated CDT and DNAzyme-mediated gene therapy to suppress tumor growth and metastasis. The Dz-MnO<sub>2</sub> nanosheets respond effectively to the TME, releasing Mn<sup>2+</sup> and DNAzyme. The DNAzyme exhibits mRNA cleavage activity, specifically targeting oncogenic transcripts to reduce tumor progression. Mn<sup>2+</sup> not only facilitates a Fenton-like reaction, enhancing the chemodynamic treatment effect, but also serves as a cofactor for DNAzyme, improving its catalytic efficiency. Concurrently, the nanosheets robustly silence the Twist1 gene, mitigating the EMT process and reinforcing CDT efficacy by suppressing apoptosis resistance. Results indicate that Dz-MnO<sub>2</sub> nanosheets efficiently polarize M2-tumor-associated macrophages (TAMs) into M1-TAMs by locally mitigating tumor hypoxia via catalyzing the decomposition of H<sub>2</sub>O<sub>2</sub> into O<sub>2</sub>. This collaborative strategy presents a promising approach to enhance CDT, effectively inhibiting tumor recurrence and metastasis.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"DNA-templated nanosheets for enhanced chemodynamic therapy and gene therapy to inhibit tumor recurrence and metastasis.\",\"authors\":\"Danna Sun, Yuwei Song, Wenyan Gao, Boyang Lin, Bei Wang, Xinjian Yang, Shaochun Li, Yi Jin, Jinchao Zhang\",\"doi\":\"10.1016/j.ijpharm.2024.124910\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Recurrence and metastasis stand as the primary contributors to mortality among patients with triple-negative breast cancer post-surgery, presenting a formidable clinical obstacle. Chemodynamic therapy (CDT), leveraging metal-ion-mediated Fenton-like reactions within the tumor microenvironment (TME), emerges as a promising avenue for addressing cancer metastasis. Despite recent progress, challenges such as tumor cell antioxidant defenses and epithelial-mesenchymal transition (EMT) impede the efficacy of CDT. Here, we introduce a novel approach using DNA-templated nanosheets (Dz-MnO<sub>2</sub>) that combine the functions of Mn<sup>2+</sup>-mediated CDT and DNAzyme-mediated gene therapy to suppress tumor growth and metastasis. The Dz-MnO<sub>2</sub> nanosheets respond effectively to the TME, releasing Mn<sup>2+</sup> and DNAzyme. The DNAzyme exhibits mRNA cleavage activity, specifically targeting oncogenic transcripts to reduce tumor progression. Mn<sup>2+</sup> not only facilitates a Fenton-like reaction, enhancing the chemodynamic treatment effect, but also serves as a cofactor for DNAzyme, improving its catalytic efficiency. Concurrently, the nanosheets robustly silence the Twist1 gene, mitigating the EMT process and reinforcing CDT efficacy by suppressing apoptosis resistance. Results indicate that Dz-MnO<sub>2</sub> nanosheets efficiently polarize M2-tumor-associated macrophages (TAMs) into M1-TAMs by locally mitigating tumor hypoxia via catalyzing the decomposition of H<sub>2</sub>O<sub>2</sub> into O<sub>2</sub>. 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DNA-templated nanosheets for enhanced chemodynamic therapy and gene therapy to inhibit tumor recurrence and metastasis.
Recurrence and metastasis stand as the primary contributors to mortality among patients with triple-negative breast cancer post-surgery, presenting a formidable clinical obstacle. Chemodynamic therapy (CDT), leveraging metal-ion-mediated Fenton-like reactions within the tumor microenvironment (TME), emerges as a promising avenue for addressing cancer metastasis. Despite recent progress, challenges such as tumor cell antioxidant defenses and epithelial-mesenchymal transition (EMT) impede the efficacy of CDT. Here, we introduce a novel approach using DNA-templated nanosheets (Dz-MnO2) that combine the functions of Mn2+-mediated CDT and DNAzyme-mediated gene therapy to suppress tumor growth and metastasis. The Dz-MnO2 nanosheets respond effectively to the TME, releasing Mn2+ and DNAzyme. The DNAzyme exhibits mRNA cleavage activity, specifically targeting oncogenic transcripts to reduce tumor progression. Mn2+ not only facilitates a Fenton-like reaction, enhancing the chemodynamic treatment effect, but also serves as a cofactor for DNAzyme, improving its catalytic efficiency. Concurrently, the nanosheets robustly silence the Twist1 gene, mitigating the EMT process and reinforcing CDT efficacy by suppressing apoptosis resistance. Results indicate that Dz-MnO2 nanosheets efficiently polarize M2-tumor-associated macrophages (TAMs) into M1-TAMs by locally mitigating tumor hypoxia via catalyzing the decomposition of H2O2 into O2. This collaborative strategy presents a promising approach to enhance CDT, effectively inhibiting tumor recurrence and metastasis.
期刊介绍:
The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.