RETRACTED ARTICLE: Copper-based metal–organic framework impedes triple-negative breast cancer metastasis via local estrogen deprivation and platelets blockade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. Graphical Abstract

Platelet-Based Nanoparticles with Stimuli-Responsive for Anti-Tumor Therapy

“…Ultimately, NO effectively inhibits platelet activation within the tumor in a 4T1 mammary adenocarcinoma model. 73 For platelet-membrane-coated nanoparticles, Zhang's team developed a photothermal/acid-responsive PDA@Dox NPs complex, which exhibited outstanding therapeutic effects and effectively prevented tumor recurrence in a breast cancer mouse model. 102 Zhou developed an ultrasound and GSH-responsive MM-PEG@PLTs complex.…”

Copper(ii)-MOFs for bio-applications

“…147 Abnormal estrogen levels and activated platelets are the key driving forces for TNBC metastasis. Based on this knowledge, Wang et al 148 developed a bioactive ''ion/gas'' nanogenerator, called IGBN, which is composed of a copper-based MOF and a cisplatin-arginine (Pt-Arg) prodrug to alter the tumour microenvironment that promotes metastasis. This Cu-based MOF not only serves as a drug carrier, but also specifically produces Cu 2+ in tumours, which upon catalytic oxidation reduces estrogen levels in situ.…”

English Testing of the optimum extragent for solvent-extraction of Almaly deposit copper

“…The extraction of metals was calculated from the balance of the distribution of metals between the organic and aqueous phases. To determine the dependence of copper extraction on various parameters, 25 cm3 of a freshly prepared solution of copper sulfate with a concentration of 4 g/dm3 were mixed for 5 minutes with 10% extractants dissolved in kerosene [ [18], [19], [20]].…”