Paradoxical cell targeting of calreticulin-empowered, protein-only nanoparticles
Por:
Parladé, E, García-Leon, A, Voltà-Durán, E, Unzueta, U, Mangues, R, Casanova, I, Villaverde, A, Váquez, E
Publicada:
1 sep 2024
Ahead of Print:
1 jul 2024
Resumen:
Surface-exposed calreticulin (CRT) serves as a crucial cell damage-associated molecular pattern for immunogenic apoptosis, by generating an "eat me" signal to macrophages. Aiming at precision immunotherapies we intended to artificially label tumoral cells in vivo with a recombinant CRT, in a targeted way. For that, we have constructed a CRT fusion protein intended to surface attach CXCR4 + cancer cells, to stimulate their immunological destruction. As a targeting ligand of the CRT construct and to drive its specific cell adhesion, we used the peptide V1, a derivative of the vMIP-II cytokine and an antagonist of CXCR4. The modular protein tends to self-assemble as regular 16 nm nanoparticles, assisted by ionic Zn. Through both in vivo and in vitro experiments, we have determined that CRT itself confers cell targeting capabilities to the construct overcoming those of V1, that are only moderate. In particular, CRT binds HeLa cells in absence of further internalization, by a route fully independent of CXCR4. Furthermore, by cytometry in THP-1 cells, we observed that the binding of the protein is preferential for dead cells over live cells, a fact that cannot be associated to a mere artefactual adsorption. These data are discussed in the context of the oligomerizing properties of CRT and the potential clinical applicability of proteins and protein materials functionalized with this novel cell surface ligand.
Filiaciones:
Parladé, E:
Univ Autonoma Barcelona, Inst Biotecnol Biomed i, Placa Civ S-N, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, C Monforte Lemos 3-5, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Genet Microbiol, Placa Civ S-N, Barcelona 08193, Spain
García-Leon, A:
CIBER Bioingn Biomat & Nanomed CIBER BBN, C Monforte Lemos 3-5, Madrid 28029, Spain
Inst Recerca St Pau IR ST PAU, St Quinti 77-79, Barcelona 08041, Spain
Josep Carreras Leukaemia Res Inst IJC, Carretera Can Ruti, Badalona 08916, Barcelona, Spain
Voltà-Durán, E:
Univ Autonoma Barcelona, Inst Biotecnol Biomed i, Placa Civ S-N, Barcelona 08193, Spain
Unzueta, U:
CIBER Bioingn Biomat & Nanomed CIBER BBN, C Monforte Lemos 3-5, Madrid 28029, Spain
Inst Recerca St Pau IR ST PAU, St Quinti 77-79, Barcelona 08041, Spain
Josep Carreras Leukaemia Res Inst IJC, Carretera Can Ruti, Badalona 08916, Barcelona, Spain
Univ Autonoma Barcelona, Dept Genet Microbiol, Placa Civ S-N, Barcelona 08193, Spain
Mangues, R:
CIBER Bioingn Biomat & Nanomed CIBER BBN, C Monforte Lemos 3-5, Madrid 28029, Spain
Inst Recerca St Pau IR ST PAU, St Quinti 77-79, Barcelona 08041, Spain
Josep Carreras Leukaemia Res Inst IJC, Carretera Can Ruti, Badalona 08916, Barcelona, Spain
Casanova, I:
CIBER Bioingn Biomat & Nanomed CIBER BBN, C Monforte Lemos 3-5, Madrid 28029, Spain
Inst Recerca St Pau IR ST PAU, St Quinti 77-79, Barcelona 08041, Spain
Josep Carreras Leukaemia Res Inst IJC, Carretera Can Ruti, Badalona 08916, Barcelona, Spain
Villaverde, A:
Univ Autonoma Barcelona, Inst Biotecnol Biomed i, Placa Civ S-N, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, C Monforte Lemos 3-5, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Genet Microbiol, Placa Civ S-N, Barcelona 08193, Spain
Váquez, E:
Univ Autonoma Barcelona, Inst Biotecnol Biomed i, Placa Civ S-N, Barcelona 08193, Spain
CIBER Bioingn Biomat & Nanomed CIBER BBN, C Monforte Lemos 3-5, Madrid 28029, Spain
Univ Autonoma Barcelona, Dept Genet Microbiol, Placa Civ S-N, Barcelona 08193, Spain
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