title: Hydrophobic interaction mediating self-assembled nanoparticles of succinobucol suppress lung metastasis of breast cancer by inhibition of VCAM-1 expression.
abstract: The prevention and treatment of lung metastasis of breast cancer remain a major challenge. The vascular cell adhesion molecule-1 (VCAM-1) could provide a potential therapeutic target in lung metastasis. Herein, succinobucol (SCB), a water-insoluble potent and selective VCAM-1 inhibitor, was assembled with triblock polymer poloxamer P188 into nanoparticles due to the intermolecular hydrophobic interactions. The experimental results showed that the SCB loaded nanoparticles (SN) could greatly improve the oral delivery and suppress the lung metastasis of breast cancer. The cell migration and invasion abilities of metastatic 4T1 breast cancer cells were obviously inhibited by SN. Moreover, the VCAM-1 expression on 4T1 cells was significantly reduced by SN, and the cell-cell binding ratio of RAW 264.7 cells to 4T1 cells greatly decreased from 47.4% to 3.2%. Furthermore, the oral bioavailability of SCB was greatly improved about 13-fold by SN, and the biodistribution in major organs was evidently enhanced. In particular, in the metastatic breast cancer model, the lung metastasis was notably reduced by SN treatment, and the VCAM-1 expression in lung tissues was significantly inhibited. Thereby, SN could evoke a new effective therapeutic efficacy of SCB on lung metastasis of breast cancer by inhibition of VCAM-1 expression.
authors.affiliation: State key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Haiqiang
authors.initials: H
authors.lastname: Cao
authors.affiliation: State key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China. Electronic address: zwzhang0125@simm.ac.cn.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China; Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: State key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: He
authors.affiliation: State key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Yu
authors.affiliation: State key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Wangwen
authors.initials: W
authors.lastname: Gu
authors.affiliation: State key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Lingli
authors.initials: L
authors.lastname: Chen
authors.affiliation: State key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China. Electronic address: ypli@simm.ac.cn.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001682:Biological Availability; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005260:Female; D057927:Hydrophobic and Hydrophilic Interactions; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050997:Nanomedicine; D053758:Nanoparticles; D009361:Neoplasm Invasiveness; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry*; D011341:Probucol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D019010:Vascular Cell Adhesion Molecule-1; D020442:Poloxamer; C471047:succinobucol; D011341:Probucol
keywords: Breast cancer; Cancer metastasis; Nanoparticles; Oral delivery; Succinobucol; VCAM-1