THE INFLUENCE OF SURFACE CHEMISTRY AND PROTEIN CORONA IN THE CELLULAR UPTAKE OF NON-TARGETED POLYMERIC NANOPARTICLES

• Grant number: 15/24686-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2016
• End date: September 30, 2019
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
• Principal Investigator: Fernando Carlos Giacomelli
• Grantee: Carlos Eduardo de Castro
• 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 devoted to cellular uptake of nanoscale structures and the influence of the protein corona on the phenomenon. Initially, a library of coumarin-6 loaded polymeric nanoparticles will be manufactured from the pH-responsive and biocompatible block copolymers PEOm-b-PDPAn, PMPCm-b-PDPAn e PHPMAm-b-PDPAn. They will be further deeply characterized by using essentially scattering techniques (dynamic light scattering - DLS, static light scattering - SLS and electrophoretic light scattering - ELS) besides atomic force microscopy - AFM. Subsequently it will be evaluated the cellular uptake of the produced entities and the relation with their structural features, particularly the nature of the hydrophilic stabilizing shell (PEO, PMPC and PHPMA). These investigations will be performed using the resources of flow cytometry (FACS) and laser scanning confocal microscopy (LSCM). Afterwards, the focus will be moved to the protein corona formation. The produced nanoparticles will be incubated in plasma environment and by using centrifugation, Polyacrylamide gel electrophoresis (SDS-PAGE) and Liquid chromatography-mass spectrometry (LC-MS) it will be identified and quantified the adsorbed macromolecules in distinct entities. The cellular uptake of the protein-nanoparticle complexes will be further investigated in order to shed some light on its effect on the cell internalization process. Finally, similar evaluation will be conducted in the surface functionalized entity RGD-PHPMAm-b-PDPAn. The entity will be functionalized by using the peptide sequence Arginylglycylaspartic acid (RGD). This is a tripeptide composed of L-arginine, glycine, and L-aspartic acid and the sequence is a common element in cellular recognition.

Scientific publications

(9)

(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)

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)

DE CASTRO, CARLOS E.; RIBEIRO, CAROLINE A. S.; ALAVARSE, ALEX C.; ALBUQUERQUE, LINDOMAR J. C.; DA SILVA, MARIA C. C.; JAEGER, ELIEZER; SURMAN, FRANTISEK; SCHMIDT, VANESSA; GIACOMELLI, CRISTIANO; GIACOMELLI, FERNANDO C.. Nanoparticle-Cell Interactions: Surface Chemistry Effects on the Cellular Uptake of Biocompatible Block Copolymer Assemblies. Langmuir, v. 34, n. 5, p. 2180-2188, FEB 6 2018. (15/24686-4, 17/00459-4)

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)

DE CASTRO, CARLOS E.; RIBEIRO, CAROLINE A. S.; DA SILVA, MARIA C. C.; DAL-BO, ALEXANDRE GONCALVES; GIACOMELLI, FERNANDO C.. Sweetness Reduces Cytotoxicity and Enables Faster Cellular Uptake of Sub-30 nm Amphiphilic Nanoparticles. Langmuir, v. 35, n. 24, p. 8060-8067, JUN 18 2019. (15/24686-4, 17/00459-4)

DE CASTRO, CARLOS E.; PANICO, KARINE; STANGHERLIN, LUCAS M.; ALBUQUERQUE, LINDOMAR J. C.; A. S. RIBEIRO, CAROLINE; DA SILVA, MARIA C. C.; JAGER, ELIEZER; GIACOMELLI, FERNANDO C.. Evidence of protein coronas around soft nanoparticles regardless of the chemical nature of the outer surface: structural features and biological consequences. JOURNAL OF MATERIALS CHEMISTRY B, v. 9, n. 8, p. 2073-2083, FEB 28 2021. (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. 11-pg., 2017-09-01. (15/24686-4, 14/22983-9, 14/22322-2)

DE CASTRO, CARLOS E.; PANICO, KARINE; STANGHERLIN, LUCAS M.; RIBEIRO, CAROLINE A. S.; DA SILVA, MARIA C. C.; CARNEIRO-RAMOS, MARCELA S.; DAL-BO, ALEXANDRE G.; GIACOMELLI, FERNANDO C.. The Protein Corona Conundrum: Exploring the Advantages and Drawbacks of its Presence around Amphiphilic Nanoparticles. BIOCONJUGATE CHEMISTRY, v. 31, n. 11, p. 2638-2647, NOV 18 2020. (19/06634-8, 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)

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)