Recruiting potent membrane penetrability in tumor cell-targeted protein-only nanoparticles
Por:
Serna, N, Sanchez, JM, Unzueta, U, Sanchez-Garcia, L, Sanchez-Chardi, A, Mangues, R, Vazquez, E, Villaverde, A
Publicada:
15 mar 2019
Resumen:
The membrane pore-forming activities of the antimicrobial peptide GWH1 have been evaluated in combination with the CXCR4-binding properties of the peptide T22, in self-assembling protein nanoparticles with high clinical potential. The resulting materials, of 25 nm in size and with regular morphologies, show a dramatically improved cell penetrability into CXCR4(+) cells (more than 10-fold) and enhanced endosomal escape (the lysosomal degradation dropping from 90% to 50%), when compared with equivalent protein nanoparticles lacking GWH1. These data reveal that GWH1 retains its potent membrane activity in form of nanostructured protein complexes. On the other hand, the specificity of T22 in the CXCR4 receptor binding is subsequently minimized but, unexpectedly, not abolished by the presence of the antimicrobial peptide. The functional combination T22-GWH1 results in 30% of the nanoparticles entering cells via CXCR4 while also exploiting pore-based uptake. Such functional materials are capable to selectively deliver highly potent cytotoxic drugs upon chemical conjugation, promoting CXCR4-dependent cell death. These data support the further development of GWH1-empowered cell-targeted proteins as nanoscale drug carriers for precision medicines. This is a very promising approach to overcome lysosomal degradation of protein nanostructured materials with therapeutic value.
Filiaciones:
Serna, N:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, E-08193 Barcelona, Spain
Sanchez, JM:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
Univ Nacl Cordoba, CONICET, IIBYT, ICTA, Av Velez Sarsfield 1611,X 5016GCA, Cordoba, Argentina
UNC, FCEFyN, Dept Quim, Catedra Quim Biol, Av Velez Sarsfield 1611,X 5016GCA, Cordoba, Argentina
Unzueta, U:
CIBER Bioingn Biomat & Nanomed CIBER BBN, E-08193 Barcelona, Spain
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, E-08025 Barcelona, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, E-08025 Barcelona, Spain
Sanchez-Garcia, L:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, E-08193 Barcelona, Spain
Sanchez-Chardi, A:
Univ Autonoma Barcelona, Serv Microscopia, E-08193 Barcelona, Spain
Mangues, R:
CIBER Bioingn Biomat & Nanomed CIBER BBN, E-08193 Barcelona, Spain
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, E-08025 Barcelona, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, E-08025 Barcelona, Spain
Vazquez, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, E-08193 Barcelona, Spain
Villaverde, A:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, E-08193 Barcelona, Spain
Green Accepted
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