title: Synergistic inhibition of breast cancer metastasis by silibinin-loaded lipid nanoparticles containing TPGS.
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.
authors.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Xu
authors.forename: Qi
authors.initials: Q
authors.lastname: Yin
authors.forename: Jianan
authors.initials: J
authors.lastname: Shen
authors.forename: Lingli
authors.initials: L
authors.lastname: Chen
authors.forename: Haijun
authors.initials: H
authors.lastname: Yu
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D053758:Nanoparticles; D009361:Neoplasm Invasiveness; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000077385:Silybin; D012838:Silymarin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000071250:Snail Family Transcription Factors; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D010713:Phosphatidylcholines; D012838:Silymarin; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014810:Vitamin E; D011092:Polyethylene Glycols; D000077385:Silybin; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C014225:tocophersolan
keywords: Breast cancer; Metastasis; Nanoparticles; Silibinin; TPGS