title: Redox-sensitive nanoparticles from amphiphilic cholesterol-based block copolymers for enhanced tumor intracellular release of doxorubicin.
abstract: A novel amphiphilic cholesterol-based block copolymer comprised of a polymethacrylate bearing cholesterol block and a polyethylene glycol block with reducible disulfide bonds (PC5MA-SS-PEO) was synthesized and evaluated as a redox-sensitive nanoparticulate delivery system. The self-assembled PC5MA-SS-PEO nanoparticles (SS-NPs) encapsulated the anticancer drug doxorubicin (DOX) with high drug loading (18.2% w/w) and high encapsulation efficiency (94.9%). DOX-encapsulated PC5MA-SS-PEO self-assembled nanoparticles (DOX-encapsulated SS-NPs) showed excellent stability and exhibited a rapid DOX release in response to dithiothreitol reductive condition. Importantly, following internalization by lung cancer cells, the reducible DOX-encapsulated SS-NPs achieved higher cytotoxicity than the non-reducible thioester NPs whereas blank nanoparticles were non-cytotoxic. Furthermore, in vivo imaging studies in tumor-bearing severe combined immunodeficiency (SCID) mice showed that the nanoparticles preferentially accumulated in tumor tissue with remarkably reduced accumulation in the healthy non-target organs. The results indicated that the SS-NPs may be a promising platform for cancer-cell specific delivery of hydrophobic anticancer drugs.
  
  
  BACKGROUND
  The use of nanocarriers for drug delivery against tumors has been under intense research. One problem of using carrier system is the drug release kinetics at tumor site. In this article, the authors continued their previous study in the development of an amphiphilic cholesterol-based block copolymer with redox-sensitive modification, so that the payload drug could be released in response to the microenvironment. The interesting results should provide a new direction for designing future novel nanocarrier systems.
authors.affiliation: Polymer Program, Institute of Materials Science, University of Connecticut, Storrs, CT.
authors.forename: Chi Thanh
authors.initials: CT
authors.lastname: Nguyen
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, MA.
authors.forename: Thanh Huyen
authors.initials: TH
authors.lastname: Tran
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University, Boston, MA.
authors.forename: Mansoor
authors.initials: M
authors.lastname: Amiji
authors.affiliation: Polymer Program, Institute of Materials Science, University of Connecticut, Storrs, CT; Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT. Electronic address: xiuling.lu@uconn.edu.
authors.forename: Xiuling
authors.initials: X
authors.lastname: Lu
authors.affiliation: Polymer Program, Institute of Materials Science, University of Connecticut, Storrs, CT; Department of Chemistry, University of Connecticut, Storrs, CT. Electronic address: kasi@ims.uconn.edu.
authors.forename: Rajeswari M
authors.initials: RM
authors.lastname: Kasi
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002784:Cholesterol / Q000031:analogs & derivatives*; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D008297:Male; D016513:Mice, SCID; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy; D010084:Oxidation-Reduction; D011092:Polyethylene Glycols / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D004220:Disulfides; D011109:Polymethacrylic Acids; C030613:polymethacrylic acid; D011092:Polyethylene Glycols; D004317:Doxorubicin; D002784:Cholesterol
keywords: Block copolymer; Cancer therapy; Cholesterol; Intracellular release; Redox-sensitive nanoparticles