Exosome membrane-biomimetic nanomedicine targets the pre-metastatic niche via NF-κB inhibition to suppress breast cancer lung metastasis
Rui Tang, Chengyu Mao, Caofang Hu, Wei Liu, Ju Bai, Yali Wang, Lijun Yang, Hongzhao Qi
TL;DR
A new nanomedicine targets and disrupts the pre-metastatic niche in the lungs to prevent breast cancer from spreading.
Contribution
A biomimetic nanomedicine is developed to inhibit NF-κB signaling in the pre-metastatic niche, reducing lung metastasis in breast cancer.
Findings
EXO@m(PDTC) inhibits NF-κB activation in pulmonary stromal cells and reduces pro-inflammatory cytokines.
The nanomedicine significantly reduces lung metastasis in breast cancer models with minimal toxicity.
Transcriptomic analysis shows downregulation of NF-κB-related pathways like cytokine and chemokine signaling.
Abstract
Breast cancer lung metastasis remains a major cause of mortality, largely driven by the formation of a pre-metastatic niche (PMN) through inflammatory signaling. Here, we report a biomimetic nanomedicine, EXO@m(PDTC), designed to target the pulmonary PMN and inhibit metastasis via suppression of nuclear factor-κB (NF-κB) signaling. The nanoconstruct consists of pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor, encapsulated within micelles coated with exosome membranes derived from breast cancer cells. This design leverages the innate lung-homing ability of tumor exosomes, enabling precise accumulation in incipient PMNs. We demonstrate that EXO@m(PDTC) effectively inhibits NF-κB activation in multiple pulmonary stromal cell types, downregulates pro-inflammatory cytokines, and attenuates PMN formation. In both tail vein and orthotopic breast cancer models, EXO@m(PDTC) significantly…
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Taxonomy
TopicsExtracellular vesicles in disease · Nanoplatforms for cancer theranostics · Immune cells in cancer