Treating metastatic triple negative breast cancer with CD44/neuropilin dual molecular targets of multifunctional nanoparticles.

Abstract

Metastasis of cancer makes up the vast majority of cancer-related deaths, and it usually initiates from tumor cells invasiveness and develops through tumor neovasculature. In this work, we have fabricated a CD44/neuropilin dual receptor-targeting nanoparticulate system (tLyP-1-HT NPs) with endogenous or FDA approved components for treating metastatic triple negative breast cancer (TNBC). The enhanced specific targeting of tLyP-1-HT NPs to both metastatic tumor cells and metastasis-supporting tumor neovasculature was contributed by means of CD44/neuropilin dual receptor-mediated interaction. The NPs not only effectively suppress the invasive capability of tumor cells themselves, but also significantly restrain the metastasis incidence via extravasation as well as the eventual colonization in lungs. In all the three types of TNBC-bearing mice models, orthotopic, post-metastasis and metastasis prevention models, the docetaxel-loaded tLyP-1-HT NPs exhibited markedly enhanced anti-tumor and anti-metastasis efficacy. The inhibitory rates of tLyP-1-HT NPs against orthotopic tumor growth and lung metastasis achieved 79.6% and 100%, respectively. The metastasis inhibition rate and life extension rate of the tLyP-1-HT NPs against post-pulmonary metastasis mice reached 85.1% and up to 62.5%, respectively. All the results demonstrated the designed dual receptor-targeting multifunctional NPs hold great potential in treating metastatic TNBC and lung metastasis.