Synergistic inhibition of breast cancer metastasis by silibinin-loaded lipid nanoparticles containing TPGS

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Abstract

Tumor metastasis is the leading cause of breast cancer-related mortality and remains to be the principal obstacle for the successful chemotherapy of breast cancer. To block metastasis of breast cancer, silibinin-loaded lipid nanoparticles (SLNs) containing TPGS and phosphatidylcholine were designed and prepared by a thin-film hydration method. The optimized SLNs were approximately 45 nm in particle size with high stability in serum, which were further demonstrated to be efficiently uptaken by MDA-MB-231 breast cancer cells. Importantly, the SLNs could accumulate within tumor tissues with high efficiency and amounts. Compared with free silibinin, SLNs exhibited much stronger inhibitory effects on the invasion and migration of MDA-MB-231 cells through the downregulation of MMP-9 and Snail. More importantly, systematic in vivo evaluations demonstrated that SLNs treatment group resulted in 67% and 39% less pulmonary metastases formation than saline treatment group in the spontaneous and blood vessel metastasis models, respectively. Interestingly, the blank lipid nanoparticles without silibinin were also found, for the first time, to possess the efficient anti-metastatic capabilities to some extent. The biocompatibility assay reveals that SLNs treatment did not exhibit obvious systemic toxicity in two mouse models. Therefore, SLNs are the promising delivery systems against metastasis of breast cancer cells.

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