Developing Protein-Antitumoral Drug Nanoconjugates as Bifunctional Antimicrobial Agents
Por:
Serna N., Carratalá J.V., Parladé E., Sánchez-Chardi A., Aviñó A., Unzueta U., Mangues R., Eritja R., Ferrer-Miralles N., Vazquez E., Villaverde A.
Publicada:
1 ene 2020
Resumen:
A novel concept about bifunctional antimicrobial drugs, based on self-assembling protein nanoparticles, has been evaluated here over two biofilm-forming pathogens, namely Pseudomonas aeruginosa and Staphylococcus aureus. Two structurally different antimicrobial peptides (GWH1 and PaDBS1R1) were engineered to form regular nanoparticles of around 35 nm, to which the small molecular weight drug Floxuridine was covalently conjugated. Both the assembled peptides and the chemical, a conventional cytotoxic drug used in oncotherapy, showed potent antimicrobial activities that were enhanced by the combination of both molecules in single pharmacological entities. Therefore, the resulting prototypes show promises as innovative nanomedicines, being potential alternatives to conventional antibiotics. The biological performance and easy fabrication of these materials fully support the design of protein-based hybrid constructs for combined molecular therapies, expected to have broad applicability beyond antimicrobial medicines. In addition, the approach taken here validates the functional exploration and repurposing of antitumoral drugs, which at low concentrations perform well as unexpected biofilm-inhibiting agents. © 2020 American Chemical Society.
Filiaciones:
Serna N.:
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
CIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3-5, Madrid, 28029, Spain
Carratalá J.V.:
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
CIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3-5, Madrid, 28029, Spain
Parladé E.:
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
CIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3-5, Madrid, 28029, Spain
Sánchez-Chardi A.:
Servei de Microscòpia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
Departament de Biologia Evolutiva, Ecologia i Ciències Ambientals, Facultat de Biologia, Universitat de Barcelona, Av. Diagonal 643, Barcelona, 08028, Spain
Aviñó A.:
CIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3-5, Madrid, 28029, Spain
Institute for Advanced Chemistry of Catalonia (IQAC), CSIC, Barcelona, 08034, Spain
Unzueta U.:
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
CIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3-5, Madrid, 28029, Spain
Biomedical Research Institute Sant Pau (IIB Sant Pau), Sant Antoni Maria Claret 167, Barcelona, 08025, Spain
Mangues R.:
CIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3-5, Madrid, 28029, Spain
Biomedical Research Institute Sant Pau (IIB Sant Pau), Sant Antoni Maria Claret 167, Barcelona, 08025, Spain
Eritja R.:
CIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3-5, Madrid, 28029, Spain
Institute for Advanced Chemistry of Catalonia (IQAC), CSIC, Barcelona, 08034, Spain
Ferrer-Miralles N.:
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
CIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3-5, Madrid, 28029, Spain
Vazquez E.:
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
CIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3-5, Madrid, 28029, Spain
Villaverde A.:
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, 08193, Spain
CIBER de Bioingeniería Biomateriales y Nanomedicina (CIBER-BBN), C/Monforte de Lemos 3-5, Madrid, 28029, Spain
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