title: Redox-Responsive Polyphosphoester-Based Micellar Nanomedicines for Overriding Chemoresistance in Breast Cancer Cells.
abstract: Multidrug resistance (MDR) has been recognized as a key factor contributing to the failure of chemotherapy for cancer in the clinic, often due to insufficient delivery of anticancer drugs to target cells. For addressing this issue, a redox-responsive polyphosphoester-based micellar nanomedicine, which can be triggered to release transported drugs in tumor cells, has been developed. The micelles are composed of diblock copolymers with a hydrophilic PEG block and a hydrophobic polyphosphoester (PPE) block bearing a disulfide bond in a side group. After incubating the redox-responsive micelles with drug-resistant tumor cells, the intracellular accumulation and retention of DOX were significantly enhanced. Moreover, after internalization by MDR cancer cells, the disulfide bond in the side group was cleaved by the high intracellular glutathione levels, resulting in a hydrophobic to hydrophilic transition of the PPE block and subsequent disassembly of the micelles. Thus, the encapsulated DOX was rapidly released, and abrogation of drug resistance in the cancer cells was observed in vitro. Moreover, the DOX-loaded redox-responsive micelles exhibited significantly enhanced inhibition of tumor growth in nude mice bearing MCF-7/ADR xenograft tumors via tail vein injection, indicating that such micelles have great potential in overcoming MDR for cancer therapy.
authors.affiliation: School of Medical Engineering, Hefei University of Technology , Hefei, Anhui 230009, P.R. China.
authors.forename: Yin-Chu
authors.initials: YC
authors.lastname: Ma
authors.affiliation: School of Medical Engineering, Hefei University of Technology , Hefei, Anhui 230009, P.R. China.
authors.forename: Jun-Xia
authors.initials: JX
authors.lastname: Wang
authors.affiliation: School of Medical Engineering, Hefei University of Technology , Hefei, Anhui 230009, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tao
authors.affiliation: School of Life Sciences and Medical Center, University of Science & Technology of China , Hefei, Anhui 230027, P.R. China.
authors.forename: Chun-Yang
authors.initials: CY
authors.lastname: Sun
authors.affiliation: School of Life Sciences and Medical Center, University of Science & Technology of China , Hefei, Anhui 230027, P.R. China.
authors.forename: Yu-Cai
authors.initials: YC
authors.lastname: Wang
authors.affiliation: School of Medical Engineering, Hefei University of Technology , Hefei, Anhui 230009, P.R. China.
authors.forename: Dong-Dong
authors.initials: DD
authors.lastname: Li
authors.affiliation: School of Medical Engineering, Hefei University of Technology , Hefei, Anhui 230009, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Fan
authors.affiliation: School of Medical Engineering, Hefei University of Technology , Hefei, Anhui 230009, P.R. China.
authors.forename: Hai-Sheng
authors.initials: HS
authors.lastname: Qian
authors.affiliation: School of Medical Engineering, Hefei University of Technology , Hefei, Anhui 230009, P.R. China.
authors.forename: Xian-Zhu
authors.initials: XZ
authors.lastname: Yang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D000067493:Dynamic Light Scattering; D004952:Esters / Q000737:chemistry*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008823:Micelles; D050997:Nanomedicine / Q000379:methods*; D010084:Oxidation-Reduction; D011122:Polyphosphates / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy; D011721:Pyrenes / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004952:Esters; D008823:Micelles; D011122:Polyphosphates; D011721:Pyrenes; D004317:Doxorubicin; C030984:pyrene
keywords: cancer therapy; drug delivery; drug resistance; polyphosphoester; redox-responsive