Environmentally-responsive supramolecular polymeric assemblies for the intracellular delivery of therapeutic DNA: towards a toolbox for novel generation of nanopharmaceuticals in ophthalmology

• Grant number: 19/20470-8
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2021
• End date: November 30, 2023
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
• Agreement: European Commission (Horizon 2020)
• Principal Investigator: Fernando Carlos Giacomelli
• Grantee: Fernando Carlos Giacomelli
• Principal researcher abroad: Maria Vamvakaki
• Institution abroad: University of Crete, Heraklion (UoC), Greece
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

This proposal is inserted in the NanoPol Project which has been approved in Europe and receives funding from the European Union's Horizon 2020 research and innovation programme under the Marie SkBodowska-Curie Actions (MSCA) Research and Innovation Staff Exchange (RISE) H2020-MSCA-RISE-2018 Grant Agreement No 823883 (the UFABC is one of the Partner Institutions). The main objective of the NanoPol project is the creation of new knowledge in the field of polymeric drug delivery systems for ophthalmological applications. The international research network wishes to design, synthesize and study novel polymer architectures and formulations in this framework. We wish to particular focus, as a Partner Institution, in the development of novel non-viral vectors for gene therapies focused on ocular diseases. It is nowadays well accepted that a number of blinding dystrophies is linked to aberrations in the retina and genetic disorders. Accordingly, gene therapy has been identified as a favored candidate for such treatments however, gene transport into the ocular surface cell is difficult due to several physiological obstacles including the poor corneal permeability. We will evaluate evaluated the potential of surface functionalized polyplexes and stimuli-responsive polymersomes as gene-delivery platforms to human retinal pigment epithelium (RPE) cells. The polymersomes will be produced from novel synthesized pH-responsive PHPMAm-b-PDPAn block copolymers and the polyplexes will be manufactured from hydrophobically and-or sugar-modified polyethyleneimine (PEI). We target more effective cellular uptake of the assemblies and further gene transfection into hard-to-transfect human RPE cells. (AU)

Scientific publications

(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)

DE OLIVEIRA, FERNANDO A.; ALBUQUERQUE, LINDOMAR J. C.; DELECOURT, GWENDOLINE; BENNEVAULT, VERONIQUE; GUEGAN, PHILIPPE; GIACOMELLI, FERNANDO C.. Current Designs of Polymeric Platforms Towards the Delivery of Nucleic Acids Inside the Cells with Focus on Polyethylenimine. CURRENT GENE THERAPY, v. 21, n. 5, p. 431-451, 2021. (16/23844-8, 18/11038-2, 19/20470-8, 19/12944-0)

DE OLIVEIRA, FERNANDO A.; ALBUQUERQUE, LINDOMAR J. C.; NASCIMENTO-SALES, MICHELLE; CHRISTOFFOLETE, MARCELO A.; BELLETTINI, ISMAEL C.; GIACOMELLI, FERNANDO C.. Balancing gene transfection and cytotoxicity of nucleic acid carriers with focus on ocular and hepatic disorders: evaluation of hydrophobic and hydrophilic polyethyleneimine derivatives. JOURNAL OF MATERIALS CHEMISTRY B, v. 11, n. 20, p. 16-pg., 2023-04-24. (19/20470-8, 21/12071-6, 19/12944-0)

RIBEIRO, CAROLINE A. S.; ALBUQUERQUE, LINDOMAR J. C.; DE CASTRO, CARLOS E.; PEREIRA, RODRIGO M.; ALBUQUERQUE, BRUNNO L.; PAVLOVA, EWA; SCHLUTER, LUIZA GABRIELA; BATISTA, BRUNO L.; BELLETTINI, ISMAEL C.; GIACOMELLI, FERNANDO C.. eady-to-use room temperature one-pot synthesis of surface-decorated gold nanoparticles with targeting attribute. Journal of Colloid and Interface Science, v. 614, p. 489-501, MAY 15 2022. (19/20470-8)