Occam’s Razor-Inspired Nb2C delivery platform potentiates breast cancer therapy and inhibits lung metastasis

Abstract

Breast cancer exhibits a high rate of lung metastasis and is one of the leading causes of cancer-related mortality in women. Hence, it is critical to develop innovative therapeutic strategies to combat breast cancer and lung metastasis. The physical and optical properties of niobium carbide (Nb2C) nanosheets endow them with excellent photothermal conversion properties and the capacity for drug delivery, making them ideal for photothermal therapy (PTT) in breast cancer and its lung metastasis. To explore a new synergistic strategy for subcutaneous tumor ablation and lung metastasis inhibition in breast cancer, an Occam’s Razor-inspired nanocomposite (Nb2C-BBR) was fabricated based on functionalized Nb2C nanosheets and berberine (BBR), a natural inhibitor that regulates metastasis-related proteins in the tumor microenvironment. The Nb2C nanosheets were ultrathin (thickness of ∼ 124 nm), could be endocytosed into subcellular organelles, showed desirable photothermal-conversion efficiency (38 % and 59 % at 808 nm and 1064 nm, respectively), and achieved multi-modal imaging in the near-infrared (NIR-II) biowindow. With a size of 130.4 nm, the Nb2C-BBR nanocomposites exhibited favorable biocompatibility and reduced the dose of Nb2C nanosheets required under NIR-II irradiation while maintaining photothermal performance and anticancer efficacy. Combined chemotherapy and PTT with the Nb2C-BBR nanocomposites not only eradicated cancer cells notably but also significantly suppressed cell proliferation by activating the mitochondrial apoptotic pathway. By regulating the expression of proteins associated with the epithelial-mesenchymal transition and extracellular matrix both in vitro and in vivo, Nb2C-BBR nanocomposites significantly inhibited the migration and invasion of breast cancer cells following NIR-II irradiation. The functionalized nanoplatform for synergistic therapy efficiently destroyed cancer cells, inhibited metastasis, and induced only minor local tissue damage, demonstrating its potential as a treatment approach for metastatic tumors.