title: A pH-Responsive Host-guest Nanosystem Loading Succinobucol Suppresses Lung Metastasis of Breast Cancer.
abstract: Cancer metastasis is the leading reason for the high mortality of breast cancer. Herein, we report on a pH-responsive host-guest nanosystem of succinobucol (PHN) with pH-stimuli controlled drug release behavior to improve the therapeutic efficacy on lung metastasis of breast cancer. PHN was composed of the host polymer of β-cyclodextrin linked with multiple arms of N,N-diisopropylethylenediamine (βCD-DPA), the guest polymer of adamantyl end-capped methoxy poly(ethylene glycol) (mPEG-Ad), and the active agent of succinobucol. PHN comprises nanometer-sized homogenous spherical particles, and exhibits specific and rapid drug release in response to the intracellular acidic pH-stimuli. Then, the anti-metastatic efficacy of PHN is measured in metastatic 4T1 breast cancer cells, which effectively confirms the superior inhibitory effects on cell migration and invasion activities, VCAM-1 expression and cell-cell binding of RAW 264.7 to 4T1 cells. Moreover, PHN can be specifically delivered to the sites of metastatic nodules in lungs, and result in an obviously improved therapeutic efficacy on lung metastasis of breast cancer. Thereby, the pH-responsive host-guest nanosystem can be a promising drug delivery platform for effective treatment of cancer metastasis.
authors.affiliation: 1. State key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.; 2. School of Pharmacy, Shanghai Jiaotong University, Shanghai 200240, China.
authors.forename: Zhaoling
authors.initials: Z
authors.lastname: Dan
authors.affiliation: 1. 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: 1. 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: 1. 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: 2. School of Pharmacy, Shanghai Jiaotong University, Shanghai 200240, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zou
authors.affiliation: 3. School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zeng
authors.affiliation: 2. School of Pharmacy, Shanghai Jiaotong University, Shanghai 200240, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: 1. 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: 1. State key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Xu
authors.affiliation: 1. State key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Dafang
authors.initials: D
authors.lastname: Zhong
authors.affiliation: 1. 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: 2. School of Pharmacy, Shanghai Jiaotong University, Shanghai 200240, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Shen
authors.affiliation: 1. State key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: 1. 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 / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001943:Breast Neoplasms / Q000150:complications*; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D006863:Hydrogen-Ion Concentration; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry; D009361:Neoplasm Invasiveness; D011092:Polyethylene Glycols / Q000378:metabolism; D011341:Probucol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016896:Treatment Outcome; D047392:beta-Cyclodextrins / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D047392:beta-Cyclodextrins; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; C471047:succinobucol; D011341:Probucol
keywords: Breast cancer.; Cancer metastasis; Cyclodextrin; Host-guest nanosystem; pH-responsive