title: α-Tocopheryl succinate-based amphiphilic block copolymers obtained by RAFT and their nanoparticles for the treatment of cancer.
abstract: α-Tocopheryl succinate (α-TOS) is a well-known mitochondrially targeted anticancer compound. However, the major factor limiting the use of α-TOS is its low solubility in physiological media. To overcome this problem, the aim of this work is the preparation of new polymeric and active α-TOS-based nanovehicle with a precise control over its macromolecular architecture. Reversible addition-fragmentation chain transfer polymerization (RAFT) is used to synthesize an α-TOS amphiphilic block copolymer with highly homogeneous molecular weight and relatively narrow dispersity. Macro-chain transfer agents (macro-CTA) based on poly(ethylene glycol) (PEG) of different molecular weights (MW, ranging from 4.6 to 20 kDa) are used to obtain block copolymers with different hydrophilic/hydrophobic ratios with PEG being the hydrophilic block and a methacrylic derivative of α-tocopheryl succinate (MTOS) being the monomer that formed the hydrophobic block. PEG-b-poly(MTOS) form spherical nanoparticles (NPs) by self-organized precipitation (SORP) or solvent exchange in aqueous media enabling to encapsulate and deliver hydrophobic molecules in their core. The resulting NPs are rapidly endocytosed by cancer cells. The biological activity of the synthesized NPs are found to depend on the MW of PEG, with NP comprised of the higher MW copolymer resulting in the lower bioactivity due to PEG shielding inhibiting cellular uptake by endocytosis. Moreover, the biological activity also depends on the MTOS content, as the biological activity increases as a function of MTOS concentration.
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, 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, 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 Georgia, USA.
authors.forename: N 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 Georgia, 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, Spain.
authors.forename: Julio San
authors.initials: JS
authors.lastname: Román
keywords: RAFT polymerization; poly(ethylene glycol); self-assembled nanoparticle; self-organized precipitation; α-tocopheryl succinate