title: pH-Responsive Wormlike Micelles with Sequential Metastasis Targeting Inhibit Lung Metastasis of Breast Cancer.
abstract: Cancer metastasis is the main cause for the high mortality in breast cancer patients. Herein, we first report succinobucol-loaded pH-responsive wormlike micelles (PWMs) with sequential targeting capability to inhibit lung metastasis of breast cancer. PWMs can in a first step be delivered specifically to the sites of metastases in the lungs and then enable the intracellular pH-stimulus responsive drug release in cancer cells to improve the anti-metastatic effect. PWMs are identified as nanofibrillar assemblies with a diameter of 19.9 ± 1.9 nm and a length within the 50-200 nm range, and exhibited pH-sensitive drug release behavior in response to acidic intracellular environments. Moreover, PWMs can obviously inhibit the migration and invasion abilities of metastatic 4T1 breast cancer cells, and reduce the expression of the metastasis-associated vascular cell adhesion molecule-1 (VCAM-1) at 400 ng mL(-1) of succinobucol. In particular, PWMs can induce a higher specific accumulation in lung and be specifically delivered to the sites of metastases in lung, thereby leading to an 86.6% inhibition on lung metastasis of breast cancer. Therefore, the use of sequentially targeting PWMs can become an encouraging strategy for specific targeting and effective treatment of cancer metastasis.
authors.affiliation: State key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, 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, 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, China.
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Bao
authors.affiliation: State key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, 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, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yin
authors.affiliation: State key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
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, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D006863:Hydrogen-Ion Concentration; D008175:Lung Neoplasms / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D011092:Polyethylene Glycols / Q000737:chemistry; D011341:Probucol / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D019010:Vascular Cell Adhesion Molecule-1; D011092:Polyethylene Glycols; C471047:succinobucol; D011341:Probucol
keywords: breast cancer; lung metastasis; micelles; pH-responsive; sequential targeting