Gram-Negative Bacteria Targeting Mediated by Carbohydrate-Carbohydrate Interactions Induced by Surface-Modified Nanoparticles

Author(s)

Capeletti, Larissa Brentano ^{[1, 2]} ; Affonso de Oliveira, Jessica Fernando ^{[1, 2]} ; Dias Loiola, Livia Mesquita ^[1] ; Galdino, Flavia Elisa ^{[1, 2]} ; da Silva Santos, Denys Ewerton ^[3] ; Soares, Thereza Amelia ^[3] ; Freitas, Raul de Oliveira ^[4] ; Cardoso, Mateus Borba ^{[1, 2]}

Affiliation

^[1] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Nanotechnol Natl Lab LNNano, POB 6192, BR-13083970 Campinas, SP - Brazil

^[2] Univ Estadual Campinas UNICAMP, Chem Inst IQ, POB 6154, BR-13083970 Campinas, SP - Brazil

^[3] Univ Fed Pernambuco UFPE, Dept Fundamental Chem, BR-50740540 Recife, PE - Brazil

^[4] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Synchrotron Light Lab LNLS, POB 6192, BR-13083970 Campinas, SP - Brazil

• Document type: Journal article
• Source: ADVANCED FUNCTIONAL MATERIALS; v. 29, n. 48 NOV 2019.
• Web of Science Citations: 0

Abstract

Antibiotic resistant pathogens are a modern threat to the human health. As a worldwide spreading problem, there is an urgency for new strategies to minimize antibiotic resistance, particularly the super-resistant strains. Here, the efficient design of carbohydrate-coated silica nanoparticles is reported which specifically target Gram-negative bacteria cells. The system is functionalized with gluconamide moieties and demonstrates increased binding ability to the bacterial membrane, enabling controlled drug delivery onto the pathogen wall. In addition, the high stability of the nanoparticles in biological media and the lack of non-specific protein adhesion are engendered by such functionalization, which also demonstrates low cytotoxicity and hemolytic activity prevention. Local interaction between nanoparticles and the bacterium membrane is experimentally accessed at the biomolecular level unveiling a short-range chemical connection. Atomistic molecular dynamics simulations depict the rapid penetration of gluconamide in the lipopolysaccharide region of the bacterial outer membrane, corroborating the experimental findings. Thus, this novel outer membrane-targeting platform provides a new strategy to reduce drug intake and, hence, minimize bacterial resistance. (AU)

• FAPESP's process: 17/01167-7 - Silica nanoparticles functionalized with carbohydrate oligomers and their interaction with the bacterial membrane
• Grantee: Larissa Brentano Capeletti
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/22429-9 - Synthesis of mesoporous silica nanoparticles functionalized with monoclonal antibodies: an alternative to Hodgkin (HL) and anaplastic large cell CD30+ (ALCL - CD30+) lymphomas treatment
• Grantee: Jessica Fernanda Affonso de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/25406-5 - Organizing matter: colloids formed by association of surfactants, polymers and nanoparticles
• Grantee: Watson Loh
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/09555-9 - Influence of protein corona on interaction and internalization of silica nanoparticles in human cells: from two-dimensional to tri-dimensional images
• Grantee: Flávia Elisa Galdino
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/21598-0 - Functionalized silica nanoparticles: a strategy for Zika virus inactivation
• Grantee: Lívia Mesquita Dias Loiola
• Support Opportunities: Scholarships in Brazil - Post-Doctoral