title: Dual pH-sensitive micelles with charge-switch for controlling cellular uptake and drug release to treat metastatic breast cancer.
abstract: For successful chemotherapy against metastatic breast cancer, the great efforts are still required for designing drug delivery systems that can be selectively internalized by tumor cells and release the cargo in a controlled manner. In this work, the chemotherapeutic agent paclitaxel (PTX) was loaded with the dual-pH sensitive micelle (DPM), which consisted of a pH-sensitive core, an acid-cleavable anionic shell, and a polyethylene glycol (PEG) corona. In the slightly acidic environment of tumor tissues, the anionic shell was taken off, inducing the conversion of the surface charge of DPM from negative to positive, which resulted in more efficient cellular uptake, stronger cytotoxicity and higher intra-tumor accumulation of PTX in the murine breast cancer 4T1 tumor-bearing mice models compared to the micelles with irremovable anionic or non-ionic shell. Meanwhile, the pH-sensitive core endowed DPM with rapid drug release in endo/lysosomes. The inhibitory rates of DPM against tumor growth and lung metastasis achieved 77.7% and 88.3%, respectively, without significant toxicity. Therefore, DPM is a promising nanocarrier for effective therapy of metastatic breast cancer due to satisfying the requirements of both selective uptake by tumor cells and sufficient and fast intracellular drug release.
authors.affiliation: State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China.
authors.forename: Qingshuo
authors.initials: Q
authors.lastname: Meng
authors.affiliation: State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China.
authors.forename: Jinghan
authors.initials: J
authors.lastname: Su
authors.affiliation: State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China. Electronic address: qyin@simm.ac.cn.
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, 501 Haike Road, 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, 501 Haike Road, 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, 501 Haike Road, Shanghai 201203, 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, 501 Haike Road, Shanghai 201203, 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, 501 Haike Road, Shanghai 201203, China. Electronic address: ypli@simm.ac.cn.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000556:secondary*; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D004655:Emulsions / Q000737:chemistry; D005260:Female; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D055672:Static Electricity; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004655:Emulsions; D008823:Micelles; D053769:Nanocapsules; D017239:Paclitaxel
keywords: Breast cancer; Charge-switch; Metastasis; Micelle; pH-sensitive