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Reshaping Prostate Tumor Microenvironment to Suppress Metastasis via Cancer-Associated Fibroblasts Inactivation with Peptide-Assembly Based Nanosystem.

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Prostate cancer is one of the most common malignant tumors in men, and inhibiting metastasis is a key event but still a major challenge in prostate cancer treatment. Cancer-associated fibroblasts… Click to show full abstract

Prostate cancer is one of the most common malignant tumors in men, and inhibiting metastasis is a key event but still a major challenge in prostate cancer treatment. Cancer-associated fibroblasts (CAFs) play an important role in prostate tumor metastasis by shaping the malignant tumor microenvironment. Herein, we constructed a CAFs-targeting siRNA delivery system by loading the fibroblast activation protein-α (FAP-α) antibody onto the cell-penetrating peptide (CPP)-based nanoparticles, which specifically downregulated C-X-C motif chemokine ligand 12 (CXCL12) expression in CAFs. This regulation generated series of changes through inactivating CAFs so that the malignant prostate tumor microenvironment was reshaped. The tumor cell invasion, migration and tumor angiogenesis were significantly inhibited, which all contributed to the suppression of the metastasis of orthotopic prostate tumor. This tumor microenvironment reshaping strategy via CAFs targeting and inactivation provides an alternative approach for malignant prostate tumor metastasis inhibition.

Keywords: prostate tumor; metastasis; cancer; tumor microenvironment; tumor

Journal Title: ACS nano
Year Published: 2019

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