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Copper-based metal-organic framework impedes triple-negative breast cancer metastasis via local estrogen deprivation and platelets blockade.

ABSTRACT: Metastasis is one of the main causes of failure in the treatment of triple-negative breast cancer (TNBC). Abnormally estrogen level and activated platelets are the key driving forces for TNBC metastasis. Herein, an "ion/gas" bioactive nanogenerator (termed as IGBN), comprising a copper-based MOF and loaded cisplatin-arginine (Pt-Arg) prodrug is developed for metastasis-promoting tumor microenvironment reprogramming and TNBC therapy. The copper-based MOF not only serves as a drug carrier, but also specifically produces Cu²⁺ in tumors, which catalytic oxidizing estrogen to reduce estrogen levels in situ. Meanwhile, the rationally designed Pt-Arg prodrug reduced into cisplatin to significantly promote the generation of H₂O₂ in the tumor, then permitting self-augmented cascade NO gas generation by oxidizing Arg through a H₂O₂ self-supplied way, thus blocking platelet activation in tumor. We clarified that IGBN inhibited TNBC metastasis through local estrogen deprivation and platelets blockade, affording 88.4% inhibition of pulmonary metastasis in a 4T1 mammary adenocarcinoma model. Notably, the locally copper ion interference, NO gas therapy and cisplatin chemotherapy together resulted in an enhanced therapeutic efficacy in primary tumor ablation without significant toxicity. This "ion/gas" bioactive nanogenerator offers a robust and safe strategy for TNBC therapy.

SUBMITTER: Wang S

PROVIDER: S-EPMC9258064 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Pesticides are agrochemical compounds used to kill pests (insects, rodents, fungi, or unwanted plants), which are key to meet the world food demand. Regrettably, some important issues associated with their widespread/extensive use (contamination, bioaccumulation, and development of pest resistances) demand a reduction in the amount of pesticide applied in crop protection. Among the novel technologies used to combat the deterioration of our environment, metal-organic frameworks (MOFs) have emerged as innovative and promising materials in agroindustry since they possess several features (high porosity, functionalizable cavities, ecofriendly composition, etc.) that make them excellent candidates for the controlled release of pesticides. Moving toward a sustainable development, in this work, we originally describe the use of pesticides as building blocks for the MOF construction, leading to a new type of agricultural applied MOFs (or AgroMOFs). Particularly, we have prepared a novel 2D-MOF (namely, GR-MOF-7) based on the herbicide glufosinate and the widely used antibacterial and fungicide Cu2+. GR-MOF-7 crystallizes attaining a monoclinic P21/c space group, and the asymmetric unit is composed of one independent Cu2+ ion and one molecule of the Glu2- ligand. Considering the significant antibacterial activity of Cu-based compounds in agriculture, the potential combined bactericidal and herbicidal effect of GR-MOF-7 was investigated. GR-MOF-7 shows an important antibacterial activity against Staphylococcus aureus and Escherichia coli (involved in agricultural animal infections), improving the results obtained with its individual or even physical mixed precursors [glufosinate and Cu(NO3)2]. It is also an effective pesticide against germination and plant growth of the weed Raphanus sativus, an invasive species in berries and vines crops, demonstrating that the construction of MOFs based on herbicide and antibacterial/antifungal units is a promising strategy to achieve multifunctional agrochemicals. To the best of our knowledge, this first report on the synthesis of an MOF based on agrochemicals (what we have named AgroMOF) opens new ways on the safe and efficient MOF application in agriculture.

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Copper-based metal-organic framework impedes triple-negative breast cancer metastasis via local estrogen deprivation and platelets blockade.

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