Staff directory

Francesco Barbero

Doctoral Student
Marie Curie
francesco.barbero(ELIMINAR)@icn2.cat
Inorganic Nanoparticles

Publications

2017

  • Cationic liposomal vectors incorporating a bolaamphiphile for oligonucleotide antimicrobials

    Mamusa M., Sitia L., Barbero F., Ruyra A., Calvo T.D., Montis C., Gonzalez-Paredes A., Wheeler G.N., Morris C.J., McArthur M., Berti D. Biochimica et Biophysica Acta - Biomembranes; 1859 (10): 1767 - 1777. 2017. 10.1016/j.bbamem.2017.06.006. IF: 3.498

    Antibacterial resistance has become a serious crisis for world health over the last few decades, so that new therapeutic approaches are strongly needed to face the threat of resistant infections. Transcription factor decoys (TFD) are a promising new class of antimicrobial oligonucleotides with proven in vivo activity when combined with a bolaamphiphilic cationic molecule, 12-bis-THA. These two molecular species form stable nanoplexes which, however, present very scarce colloidal stability in physiological media, which poses the challenge of drug formulation and delivery. In this work, we reformulated the 12-bis-THA/TFD nanoplexes in a liposomal carrier, which retains the ability to protect the oligonucleotide therapeutic from degradation and deliver it across the bacterial cell wall. We performed a physical-chemical study to investigate how the incorporation of 12-bis-THA and TFD affects the structure of POPC- and POPC/DOPE liposomes. Analysis was performed using dynamic light scattering (DLS), ζ-potential measurements, small-angle x-ray scattering (SAXS), and steady-state fluorescence spectroscopy to better understand the structure of the liposomal formulations containing the 12-bis-THA/TFD complexes. Oligonucleotide delivery to model Escherichia coli bacteria was assessed by means of confocal scanning laser microscopy (CLSM), evidencing the requirement of a fusogenic helper lipid for transfection. Preliminary biological assessments suggested the necessity of further development by modulation of 12-bis-THA concentration in order to optimize its therapeutic index, i.e. the ratio of antibacterial activity to the observed cytotoxicity. In summary, POPC/DOPE/12-bis-THA liposomes appear as promising formulations for TFD delivery. © 2017 Elsevier B.V.


  • Formation of the Protein Corona: The Interface between Nanoparticles and the Immune System

    Barbero F., Russo L., Vitali M., Piella J., Salvo I., Borrajo M.L., Busquets-Fité M., Grandori R., Bastús N.G., Casals E., Puntes V. Seminars in Immunology; 34: 52 - 60. 2017. 10.1016/j.smim.2017.10.001. IF: 9.611

    The interaction of inorganic nanoparticles and many biological fluids often withstands the formation of a Protein Corona enveloping the nanoparticle. This Protein Corona provides the biological identity to the nanoparticle that the immune system will detect. The formation of this Protein Corona depends not only on the composition of the nanoparticle, its size, shape, surface state and exposure time, but also on the type of media, nanoparticle to protein ratio and the presence of ions and other molecular species that interfere in the interaction between proteins and nanoparticles. This has important implications on immune safety, biocompatibility and the use of nanoparticles in medicine. © 2017 Elsevier Ltd


  • Inclusion of oligonucleotide antimicrobials in biocompatible cationic liposomes: A structural study

    Mamusa M., Barbero F., Montis C., Cutillo L., Gonzalez-Paredes A., Berti D. Journal of Colloid and Interface Science; 508: 476 - 487. 2017. 10.1016/j.jcis.2017.08.080. IF: 4.233

    Hypothesis Transcription factor decoys (TFD) are short oligonucleotides designed to block essential genetic pathways in bacteria and defeat resistant infections. TFD protection in biological fluids and their delivery to the site of infection require formulation in appropriate delivery systems. In this work, we build on a classical phosphatidylcholine/phosphatidylethanolamine (POPC/DOPE) scaffold to design TFD-loaded cationic liposomes by combining the DNA-complexing abilities of a bolaamphiphile, (1,1′-(dodecane-1,12-diyl)-bis-(9-amino-1,2,3,4-tetrahydroacridinium) chloride (12-bis-THA), with the biocompatible cationic lipid ethyl-phosphatidylcholine (DPePC). The goal is to perform a structural study to determine the impact of the bolaamphiphile and TFD incorporation on the liposome structure, the capacity for TFD encapsulation, and the colloidal stability in saline media and cell culture environments. Experiments The systems are characterized by means of dynamic light scattering, small-angle X-ray scattering, and ζ-potential measurements, to provide a clear picture of the liposome structure. Circular dichroism (CD) spectroscopy is used to assess the compaction of the oligonucleotide in a psi form, while steady-state fluorescence and fluorescence correlation spectroscopies give insight into the entrapment rate and distribution of the TFD in the liposomes. Findings We found that the combination of the two cationic species, 12-bis-THA and DPePC, allows encapsulation of 90% of the TFD. Results of CD experiments revealed that the TFD is condensed, therefore likely protected from the lytic action of serum nucleases. Finally, the systems showed colloidal stability in aqueous dispersion with ionic strength comparable to biologically relevant media. © 2017 Elsevier Inc.