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Polyphenolic Polymersomes of Temperature-Sensitive Poly(N-vinylcaprolactam)-block-Poly(N-vinylpyrrolidone) for Anticancer Therapy.
Kozlovskaya, Veronika; Liu, Fei; Xue, Bing; Ahmad, Fahim; Alford, Aaron; Saeed, Mohammad; Kharlampieva, Eugenia.
Afiliação
  • Kozlovskaya V; Department of Chemistry, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
  • Liu F; Department of Chemistry, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
  • Xue B; Department of Chemistry, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
  • Ahmad F; Department of Infectious Disease, Drug Discovery Division, Southern Research , Birmingham, Alabama 35205, United States.
  • Alford A; Department of Chemistry, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
  • Saeed M; Department of Infectious Disease, Drug Discovery Division, Southern Research , Birmingham, Alabama 35205, United States.
  • Kharlampieva E; Department of Chemistry, University of Alabama at Birmingham , Birmingham, Alabama 35294, United States.
Biomacromolecules ; 18(8): 2552-2563, 2017 Aug 14.
Article em En | MEDLINE | ID: mdl-28700211
We report a versatile synthesis for polyphenolic polymersomes of controlled submicron (<500 nm) size for intracellular delivery of high and low molecular weight compounds. The nanoparticles are synthesized by stabilizing the vesicular morphology of thermally responsive poly(N-vinylcaprolactam)n-b-poly(N-vinylpyrrolidone)m (PVCLn-PVPONm) diblock copolymers with tannic acid (TA), a hydrolyzable polyphenol, via hydrogen bonding at a temperature above the copolymer's lower critical solution temperature (LCST). The PVCL179-PVPONm diblock copolymers are produced by controlled reversible addition-fragmentation chain transfer (RAFT) polymerization of PVPON using PVCL as a macro-chain transfer agent. The size of the TA-locked (PVCL179-PVPONm) polymersomes at room temperature and upon temperature variations are controlled by the PVPON chain length and TA:PVPON molar unit ratio. The particle diameter decreases from 1000 to 950, 770, and 250 nm with increasing PVPON chain length (m = 107, 166, 205, 234), and it further decreases to 710, 460, 290, and 190 nm, respectively, upon hydrogen bonding with TA at 50 °C. Lowering the solution temperature to 25 °C results in a slight size increase for vesicles with longer PVPON. We also show that TA-locked polymersomes can encapsulate and store the anticancer drug doxorubicin (DOX) and higher molecular weight fluorescein isothiocyanate (FITC)-dextran in a physiologically relevant pH and temperature range. Encapsulated DOX is released in the nuclei of human alveolar adenocarcinoma tumor cells after 6 h incubation via biodegradation of the TA shell with the cytotoxicity of DOX-loaded polymersomes being concentration-dependent. Our approach offers biocompatible and intracellular degradable nanovesicles of controllable size for delivery of a variety of encapsulated materials. Considering the particle monodispersity, high loading capacity, and a facile two-step aqueous assembly based on the reversible temperature-responsiveness of PVCL, these polymeric vesicles have significant potential as novel drug nanocarriers and provide a new perspective for fundamental studies on thermo-triggered polymer assemblies in solutions.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Polímeros / Caprolactama / Portadores de Fármacos / Doxorrubicina / Povidona / Adenocarcinoma Bronquioloalveolar / Polifenóis / Neoplasias Pulmonares / Antineoplásicos Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Revista: Biomacromolecules Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Polímeros / Caprolactama / Portadores de Fármacos / Doxorrubicina / Povidona / Adenocarcinoma Bronquioloalveolar / Polifenóis / Neoplasias Pulmonares / Antineoplásicos Tipo de estudo: Diagnostic_studies Limite: Humans Idioma: En Revista: Biomacromolecules Ano de publicação: 2017 Tipo de documento: Article