In Vivo Architectonic Stability of Fully de Novo Designed Protein-Only Nanoparticles
Por:
Cespedes, MV, Unzueta, U, Tatkiewicz, W, Sanchez-Chardi, A, Conchillo-Sole, O, Alamo, P, Xu, ZK, Casanova, I, Corchero, JL, Pesarrodona, M, Cedano, J, Daura, X, Ratera, I, Veciana, J, Ferrer-Miralles, N, Vazquez, E, Villaverde, A, Mangues, R
Publicada:
1 may 2014
Resumen:
The fully de novo design of protein building blocks for self-assembling as functional nanoparticles is a challenging task in emerging nanomedicines, which urgently demand novel, versatile, and biologically safe vehicles for imaging, drug delivery, and gene therapy. While the use of viruses and virus-like particles is limited by severe constraints, the generation of protein-only nanocarriers is progressively reachable by the engineering of protein protein Interactions, resulting in self-assembling functional building blocks. In particular, end-terminal cationic peptides drive the organization of structurally diverse protein species as regular nanosized oligomers, offering promise in the rational engineering of protein self-assembling. However, the in vivo stability of these constructs, being a critical issue for their medical applicability, needs to be assessed. We have explored here if the cross-molecular contacts between protein monomers, generated by end-terminal cationic peptides and oligohistidine tags, are stable enough for the resulting nanoparticles to overcome biological barriers in assembled form. The analyses of renal clearance and biodistribution of several tagged modular proteins reveal long-term architectonic stability, allowing systemic circulation and tissue targeting in form of nanoparticulate material. This observation fully supports the value of the engineered of protein building blocks addressed to the biofabrication of smart, robust, and multifunctional nanoparticles with medical applicability that mimic structure and functional capabilities of viral capsids.
Filiaciones:
Cespedes, MV:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB SantPau, Oncogenesis & Antitumor Drug Grp, Barcelona 08025, Catalonia, Spain
CIBER BBN, Barcelona 08193, Catalonia, Spain
Unzueta, U:
CIBER BBN, Barcelona 08193, Catalonia, Spain
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Catalonia, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Catalonia, Spain
Tatkiewicz, W:
CIBER BBN, Barcelona 08193, Catalonia, Spain
CSIC, Inst Ciencia Mat Barcelona, Dept Mol Nanosci & Organ Mat, E-08193 Barcelona, Catalonia, Spain
Sanchez-Chardi, A:
Univ Autonoma Barcelona, Serv Microscopia, E-08193 Barcelona, Catalonia, Spain
Conchillo-Sole, O:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Catalonia, Spain
Alamo, P:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB SantPau, Oncogenesis & Antitumor Drug Grp, Barcelona 08025, Catalonia, Spain
CIBER BBN, Barcelona 08193, Catalonia, Spain
Xu, ZK:
CIBER BBN, Barcelona 08193, Catalonia, Spain
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Catalonia, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Catalonia, Spain
Casanova, I:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB SantPau, Oncogenesis & Antitumor Drug Grp, Barcelona 08025, Catalonia, Spain
CIBER BBN, Barcelona 08193, Catalonia, Spain
Corchero, JL:
CIBER BBN, Barcelona 08193, Catalonia, Spain
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Catalonia, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Catalonia, Spain
Pesarrodona, M:
CIBER BBN, Barcelona 08193, Catalonia, Spain
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Catalonia, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Catalonia, Spain
Cedano, J:
Univ Republ, Immunol Lab, Reg Norte 50000, Salto, Uruguay
Daura, X:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Catalonia, Spain
ICREA, Barcelona 08010, Catalonia, Spain
Ratera, I:
CIBER BBN, Barcelona 08193, Catalonia, Spain
CSIC, Inst Ciencia Mat Barcelona, Dept Mol Nanosci & Organ Mat, E-08193 Barcelona, Catalonia, Spain
Veciana, J:
CIBER BBN, Barcelona 08193, Catalonia, Spain
CSIC, Inst Ciencia Mat Barcelona, Dept Mol Nanosci & Organ Mat, E-08193 Barcelona, Catalonia, Spain
Ferrer-Miralles, N:
CIBER BBN, Barcelona 08193, Catalonia, Spain
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Catalonia, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Catalonia, Spain
Vazquez, E:
CIBER BBN, Barcelona 08193, Catalonia, Spain
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Catalonia, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Catalonia, Spain
Villaverde, A:
CIBER BBN, Barcelona 08193, Catalonia, Spain
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, E-08193 Barcelona, Catalonia, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, E-08193 Barcelona, Catalonia, Spain
Mangues, R:
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB SantPau, Oncogenesis & Antitumor Drug Grp, Barcelona 08025, Catalonia, Spain
CIBER BBN, Barcelona 08193, Catalonia, Spain
Green Accepted
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