The Multifunctional Micellar System with Matrix Metalloproteinases for Metastatic Breast Cancer Therapy

The multifunctional micellar system loading traditional chemotherapeutic agent paclitaxel (PTX) and marimastat (MATT) triggered by a matrix metalloproteinases (MMPs) has been proven to have the ability to restrain tumor growth and metastasis. The self-assembly of micelles was achieved by the conjugate synthesized with an MMPs sensitive peptide as the bridge between PTX and polyethylene glycol (PEG). The researchers selected 4T1 cell line from a murine breast tumor as the cell model due to its high metastasis.

The analysis of cytotoxicity assay and cell apoptosis showed that the sensitive micelles increased toxicity and cell apoptosis, rather than the insensitive micelles. In addition, the system was shown the abilities of high penetration in tumor spheroids and significant invasion inhibition through transwell invasion assay. Furthermore, the system inhibited the growth of the metastatic tumor and prevented the lung metastasis with low systemic toxicity in the BALB/c mice bearing 4T1 tumors. The expression of MMP-2 and MMP-9 which play an important role in the tumor metastasis process was down-regulated.

All in all, both of the in vivo and in vitro studies revealed that the co-delivery of PTX and MATT by the MMPs sensitive micelles has obvious anti-tumor and tumor metastasis inhibition effect which can cause cancer death. The functional particle system will be a promising field for the future metastatic breast cancer therapy.

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