title: Enhanced Bioactivity of α-Tocopheryl Succinate Based Block Copolymer Nanoparticles by Reduced Hydrophobicity.
abstract: Well-structured amphiphilic copolymers are necessary to obtain self-assembled nanoparticles (NPs) based on synthetic polymers. Highly homogeneous and monodispersed macromolecules obtained by controlled polymerization have successfully been used for this purpose. However, disaggregation of the organized macromolecules is desired when a bioactive element, such as α-tocopheryl succinate, is introduced in self-assembled NPs and this element must be exposed or released to exert its action. The aim of this work is to demonstrate that the bioactivity of synthetic NPs based on defined reversible addition-fragmentation chain transfer polymerization copolymers can be enhanced by the introduction of hydrophilic comonomers in the hydrophobic segment. The amphiphilic terpolymers are based on poly(ethylene glycol) (PEG) as hydrophilic block, and a hydrophobic block based on a methacrylic derivative of α-tocopheryl succinate (MTOS) and small amounts of 2-hydroxyethyl methacrylate (HEMA) (PEG-b-poly(MTOS-co-HEMA)). The introduction of HEMA reduces hydrophobicity and introduces "disorder" both in the homogeneous blocks and the compact core of the corresponding NPs. These NPs are able to encapsulate additional α-tocopheryl succinate (α-TOS) with high efficiency and their biological activity is much higher than that described for the unmodified copolymers, proposedly due to more efficient degradation and release of α-TOS, demonstrating the importance of the hydrophilic-hydrophobic balance.
authors.affiliation: Group of Biomaterials, Department of Polymeric Nanomaterials and Biomaterials, Institute of Polymer Science and Technology, CSIC, Juan de la Cierva 3, 28006, Madrid, Spain.|Networking Biomedical Research Centre in Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, Av. Monforte de Lemos 3-5, 28029, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Palao-Suay
authors.affiliation: Group of Biomaterials, Department of Polymeric Nanomaterials and Biomaterials, Institute of Polymer Science and Technology, CSIC, Juan de la Cierva 3, 28006, Madrid, Spain.|Networking Biomedical Research Centre in Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, Av. Monforte de Lemos 3-5, 28029, Madrid, Spain.
authors.forename: María Rosa
authors.initials: MR
authors.lastname: Aguilar
authors.affiliation: Group of Biomaterials, Department of Polymeric Nanomaterials and Biomaterials, Institute of Polymer Science and Technology, CSIC, Juan de la Cierva 3, 28006, Madrid, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Parra-Ruiz
authors.affiliation: Supramolecular Chemistry Group, Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281-S4, 9000, Ghent, Belgium.
authors.forename: Samarendra
authors.initials: S
authors.lastname: Maji
authors.affiliation: Supramolecular Chemistry Group, Department of Organic and Macromolecular Chemistry, Ghent University, Krijgslaan 281-S4, 9000, Ghent, Belgium.
authors.forename: Richard
authors.initials: R
authors.lastname: Hoogenboom
authors.affiliation: George W. Woodruff School of Mechanical Engineering and Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr NW, Atlanta, 30332, GA, USA.
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Rohner
authors.affiliation: George W. Woodruff School of Mechanical Engineering and Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr NW, Atlanta, 30332, GA, USA.
authors.forename: Susan N
authors.initials: SN
authors.lastname: Thomas
authors.affiliation: Group of Biomaterials, Department of Polymeric Nanomaterials and Biomaterials, Institute of Polymer Science and Technology, CSIC, Juan de la Cierva 3, 28006, Madrid, Spain.|Networking Biomedical Research Centre in Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, Av. Monforte de Lemos 3-5, 28029, Madrid, Spain.
authors.forename: Julio San
authors.initials: JS
authors.lastname: Román
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001672:Biocompatible Materials / Q000737:chemistry*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D003374:Coumarins / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008689:Methacrylates / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D058105:Polymerization; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism; D014407:Tumor Cells, Cultured; D024502:alpha-Tocopherol / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D001672:Biocompatible Materials; D003374:Coumarins; D008689:Methacrylates; D011108:Polymers; D013844:Thiazoles; C517282:coumarin 6; D011092:Polyethylene Glycols; C005044:hydroxyethyl methacrylate; D024502:alpha-Tocopherol
keywords: HEMA; RAFT polymerization; amphiphilic polymers; anticancer nanoparticles; terpolymers; α-tocopheryl succinate