Development of nanostructured supramolecular polymer systems based on cationic block copolymer/DNA complexation with potential application in gene delivery

• Grant number: 14/22983-9
• Support Opportunities: Regular Research Grants
• Duration: May 01, 2015 - April 30, 2017
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
• Principal Investigator: Fernando Carlos Giacomelli
• Grantee: Fernando Carlos Giacomelli
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

The investigations will be focused on the use of "Colloids in Nanomedicine". Initially, it will be explored the manufacturing of macromolecular nanostructures via the complexation of DNA with the cationic block copolymers PEO113-b-PDEAEMA50, PEO113-b-PDPA50, PEOGMA113-b-PDAMA50 and POEGMA-b-P(OEGMA-r-DEAEMA-r-DPAEMA)50. Polyplexes based on cationic block copolymers have potential application in intracellular gene delivery. The polymer/DNA complexation will be investigated by fluorescence correlation spectroscopy (FCS) and isothermal titration calorimetry (ITC). The combination of both techniques will allow the determination of structural features of the assemblies as well as thermodynamic parameters of polymer/DNA binding. Possible conformational changes in the secondary structure of the DNA chain due to the complexation will be evaluated in parallel by circular dichroism (CD) spectroscopy. The physicochemical aspects of the supramolecular polymer systems will be probed by scattering techniques: SDLS - static dynamic light scattering, ELS - electrophoretic light scattering and SAXS - small-angle X-ray scattering besides atomic force microscopy (AFM). Selected supramolecular nanostructures will be further evaluated regarding cellular uptake through flow cytometry and confocal fluorescence microscopy using YOYO-1 labelled DNA. The transfection efficiency will be evaluated by using pEGFP-N1 plasmid encoding a red-shifted variant of wild-type green fluorescence protein (GFP). NIH 3T3 fibroblasts cell line will be employed as cell culture in all biological evaluations. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DOS SANTOS, MARINALVA CARDOSO; SERAFINI MICHELETTO, YASMINE MIGUEL; DA SILVEIRA, NADYA PESCE; PINTO, LUCIANO DA SILVA; GIACOMELLI, FERNANDO CARLOS; DE LIMA, VANIA RODRIGUES; ALLIEVI FRIZON, TIAGO ELIAS; DAL-BO, ALEXANDRE GONCALVES. Self-assembled carbohydrate-based vesicles for lectin targeting. COLLOIDS AND SURFACES B-BIOINTERFACES, v. 148, p. 12-18, DEC 1 2016. (14/22983-9)

ALBUQUERQUE, LINDOMAR J. C.; DE CASTRO, CARLOS E.; RISKE, KARIN A.; CARLAN DA SILVA, MARIA C.; MURARO, PAULO I. R.; SCHMIDT, VANESSA; GIACOMELLI, CRISTIANO; GIACOMELLI, FERNANDO C.. Gene Transfection Mediated by Catiomers Requires Free Highly Charged Polymer Chains To Overcome Intracellular Barriers. Biomacromolecules, v. 18, n. 6, p. 1918-1927, JUN 2017. (14/22983-9, 15/24686-4)

BATISTA, CARIN C. S.; ALBUQUERQUE, LINDOMAR J. C.; RIBEIRO, CAROLINE A. S.; DE CASTRO, CARLOS E.; MIRANDA, ERICA G. A.; NANTES, ISELI L.; ALBUQUERQUE, BRUNNO L.; CARDOSO, MATEUS B.; GIACOMELLI, FERNANDO C.. Nano-Sized Silver Colloids Produced and Stabilized by Amino-Functionalized Polymers: Polymer Structure-Nanoparticle Features and Polymer Structure-Growth Kinetics Relationships. Journal of the Brazilian Chemical Society, v. 28, n. 9, p. 1608-1618, SEP 2017. (14/22983-9, 14/22322-2, 15/24686-4)

ALBUQUERQUE, LINDOMAR J. C.; ANNES, KELLY; MILAZZOTTO, MARCELLA P.; MATTEI, BRUNO; RISKE, KARIN A.; JAEGER, ELIEZER; PANEK, JIRI; STEPANEK, PETR; KAPUSTA, PETER; MURARO, PAULO I. R.; et al. Efficient Condensation of DNA into Environmentally Responsive Polyplexes Produced from Block Catiomers Carrying Amine or Diamine Groups. Langmuir, v. 32, n. 2, p. 577-586, JAN 19 2016. (14/22983-9)

DE CASTRO, CARLOS E.; BONVENT, JEAN-JACQUES; DA SILVA, MARIA C. C.; CASTRO, FABIANE L. F.; GIACOMELLI, FERNANDO C.. Influence of Structural Features on the Cellular Uptake Behavior of Non-Targeted Polyester-Based Nanocarriers. Macromolecular Bioscience, v. 16, n. 11, p. 1643-1652, NOV 2016. (14/22983-9, 15/24686-4)

RIBEIRO, CAROLINE A. S.; DE CASTRO, CARLOS E.; ALBUQUERQUE, LINDOMAR J. C.; BATISTA, CARIN C. S.; GIACOMELLI, FERNANDO C.. Biodegradable nanoparticles as nanomedicines: are drug-loading content and release mechanism dictated by particle density?. COLLOID AND POLYMER SCIENCE, v. 295, n. 8, p. 1271-1280, AUG 2017. (14/22983-9, 15/24686-4)