Interactions of ultrasmall gold nanoparticles with proteins and cells

• Grant number: 19/04372-6
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2019
• End date: May 31, 2021
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Alioscka Augusto Sousa
• Grantee: Alioscka Augusto Sousa
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Ultrasmall gold nanoparticles (NPs) constitute an emerging, special class of nanomaterials supporting a wide array of biomedical and basic science applications. Ultrasmall NPs can be engineered as protein mimics to interact with biomolecules and cells in a controlled manner. Nevertheless, despite all the progress so far, there is still limited understanding of several key, fundamental aspects of ultrasmall NP-protein and NP-cell interactions, particularly concerning molecular mechanisms of interactions and their functional significance. Therefore, here a set of novel biochemical, biophysical and cell biology studies is proposed to advance the fundamental knowledge of ultrasmall NP interactions in biological systems. The project is divided into three major areas of investigation. Subproject #1: Measurements of binding kinetics and computer simulations will be performed to provide novel molecular mechanistic insights into NP-protein complexation. Subproject #2: The influence of ultrasmall NP binding on the structure and function of proteins will be studied with a focus on the long-range allosteric regulation of enzymes. Subproject #3: NP interactions within the context of a higher-complexity cellular system will be investigated through the process of endocytosis with explicit consideration for the role of the cell surface glycocalyx. Initially, fluorescent polystyrene NPs will be used as a model system in the cell uptake studies, while the long-term research goal will be to study the cell interactions of fluorescent gold nanoclusters. While the three proposed subprojects will be developed as individual units, they are naturally interconnected to provide a comprehensive picture concerning the biointeractions of ultrasmall NPs with biological systems. (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)

SOUSA, ALIOSCKA A.. Impact of soft protein interactions on the excretion, extent of receptor occupancy and tumor accumulation of ultrasmall metal nanoparticles: a compartmental model simulation. RSC ADVANCES, v. 9, n. 46, p. 26927-26941, AUG 27 2019. (19/04372-6)

LIRA, ANDRE L.; FERREIRA, RODRIGO S.; OLIVA, MARIA LUIZA, V; SOUSA, ALIOSCKA A.. Regulation of Thrombin Activity with Ultrasmall Nanoparticles: Effects of Surface Chemistry. Langmuir, v. 36, n. 27, p. 11-pg., 2020-07-14. (16/25535-2, 19/04372-6)

FERREIRA, RODRIGO S.; LIRA, ANDRE L.; TORQUATO, RICARDO J. S.; SCHUCK, PETER; SOUSA, ALIOSCKA A.. Mechanistic Insights into Ultrasmall Gold Nanoparticle-Protein Interactions through Measurement of Binding Kinetics. Journal of Physical Chemistry C, v. 123, n. 46, p. 28450-28459, NOV 21 2019. (19/04372-6, 16/25535-2)

KNITTEL, LUIZA L.; ZHAO, HUAYING; NGUYEN, AI; MIRANDA, ANTONIO; SCHUCK, PETER; SOUSA, ALIOSCKA A.. Ultrasmall Gold Nanoparticles Coated with Zwitterionic Glutathione Monoethyl Ester: A Model Platform for the Incorporation of Functional Peptides. Journal of Physical Chemistry B, v. 124, n. 19, p. 3892-3902, MAY 14 2020. (19/04372-6)

FERREIRA, RODRIGO S.; LIRA, ANDRE L.; SOUSA, ALIOSCKA A.. Quantitative mechanistic model for ultrasmall nanoparticle-protein interactions. NANOSCALE, v. 12, n. 37, p. 19230-19240, OCT 7 2020. (19/04372-6, 16/25535-2)

SOUSA, ALIOSCKA A.; SCHUCK, PETER; HASSAN, SERGIO A.. Biomolecular interactions of ultrasmall metallic nanoparticles and nanoclusters. NANOSCALE ADVANCES, v. 3, n. 11, p. 2995-3027, JUN 7 2021. (19/04372-6)