Nanosponges of circulating tumor-derived exosomes for breast cancer metastasis inhibition

Abstract

Breast cancer contributes to high mortality rates as a result of metastasis. Tumor-derived exosomes facilitate the development of the premetastatic environment, interacting and inhibiting the normal function of immune cells, thereby forming an immunosuppressive microenvironment for tumor metastasis. Herein, the platelet and neutrophil hybrid cell membrane (PNM) was embellished on a gold nanocage (AuNC) surface called nanosponges and nanokillers (NSKs). NSKs can simultaneously capture and clear the circulating tumor cells (CTCs) and tumor-derived exosomes via high-affinity membrane adhesion receptors, effectively cutting off the connection between exosomes and immune cells. Bionic NSK is loaded with doxorubicin (DOX) and indocyanine green (ICG) for synergic chemo-photothermal therapy. NSKs show greater cellular uptake, deeper tumor penetration, and higher cytotoxicity to tumor cells in comparison to non-coated AuNCs or single-coated AuNCs in vitro. In vivo, the multipurpose NSKs could not only completely ablate the primary tumor but also inhibit breast cancer metastasis with high efficiency in xenograft and orthotopic breast tumor-bearing models. Thus, NSKs could be a promising nanomedicine for the future clinical intervention of breast cancer metastasis.

Keywords: Biomimetic; Breast cancer metastasis; Circulating tumor cells; Exosomes; Platelet-neutrophil hybrid membrane.