Efficient Delivery of Antimicrobial Peptides in an Innovative, Slow-Release Pharmacological Formulation
Por:
Serna, N, López-Laguna, H, Aceituno, P, Rojas-Peña, M, Parladé, E, Voltà-Durán, E, Martínez-Torró, C, Sánchez, JM, Di Somma, A, Carratalá, JV, Livieri, AL, Ferrer-Miralles, N, Vázquez, E, Unzueta, U, Roher, N, Villaverde, A
Publicada:
1 nov 2023
Resumen:
Both nanostructure and multivalency enhance the biological activities of antimicrobial peptides (AMPs), whose mechanism of action is cooperative. In addition, the efficacy of a particular AMP should benefit from a steady concentration at the local place of action and, therefore, from a slow release after a dynamic repository. In the context of emerging multi-resistant bacterial infections and the urgent need for novel and effective antimicrobial drugs, we tested these concepts through the engineering of four AMPs into supramolecular complexes as pharmacological entities. For that purpose, GWH1, T22, Pt5, and PaD, produced as GFP or human nidogen-based His-tagged fusion proteins, were engineered as self-assembling oligomeric nanoparticles ranging from 10 to 70 nm and further packaged into nanoparticle-leaking submicron granules. Since these materials slowly release functional nanoparticles during their time-sustained unpacking, they are suitable for use as drug depots in vivo. In this context, a particular AMP version (GWH1-NIDO-H6) was selected for in vivo validation in a zebrafish model of a complex bacterial infection. The GWH1-NIDO-H6-secreting protein granules are protective in zebrafish against infection by the multi-resistant bacterium Stenotrophomonas maltophilia, proving the potential of innovative formulations based on nanostructured and slowly released recombinant AMPs in the fight against bacterial infections.
Filiaciones:
Serna, N:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed IBB, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Bioingn Biomat & Nanomed, Barcelona 08193, Spain
López-Laguna, H:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed IBB, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Bioingn Biomat & Nanomed, Barcelona 08193, Spain
Aceituno, P:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed IBB, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Biol Cellular Fisiol & Immunol, Barcelona 08193, Spain
Rojas-Peña, M:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed IBB, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Biol Cellular Fisiol & Immunol, Barcelona 08193, Spain
Parladé, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed IBB, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Bioingn Biomat & Nanomed, Barcelona 08193, Spain
Voltà-Durán, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed IBB, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Bioingn Biomat & Nanomed, Barcelona 08193, Spain
Martínez-Torró, C:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed IBB, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Bioingn Biomat & Nanomed, Barcelona 08193, Spain
Sánchez, JM:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed IBB, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Bioingn Biomat & Nanomed, Barcelona 08193, Spain
Univ Nacl Cordoba, Inst Invest Biol & Tecnol, IIByT CONICET, ICTA,FCEFyN,UNC, Ave Velez Sarsfield 1611, RA-5016 Cordoba, Argentina
Di Somma, A:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed IBB, Barcelona 08193, Spain
Carratalá, JV:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed IBB, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Bioingn Biomat & Nanomed, Barcelona 08193, Spain
Livieri, AL:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed IBB, Barcelona 08193, Spain
Ferrer-Miralles, N:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed IBB, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Bioingn Biomat & Nanomed, Barcelona 08193, Spain
Vázquez, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed IBB, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Bioingn Biomat & Nanomed, Barcelona 08193, Spain
Unzueta, U:
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Bioingn Biomat & Nanomed, Barcelona 08193, Spain
Biomed Res Inst St Pau IIB St Pau, Barcelona 08041, Spain
Roher, N:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed IBB, Barcelona 08193, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Bioingn Biomat & Nanomed, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Biol Cellular Fisiol & Immunol, Barcelona 08193, Spain
Villaverde, A:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed IBB, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Bioingn Biomat & Nanomed, Barcelona 08193, Spain
gold, All Open Access; Gold Open Access; Green Open Access
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