Engineering Protein Venoms as Self-Assembling CXCR4-Targeted Cytotoxic Nanoparticles
Por:
Serna, N, Cano-Garrido, O, Sanchez-Garcia, L, Pesarrodona, M, Unzueta, U, Sanchez-Chardi, A, Mangues, R, Vazquez, E, Villaverde, A
Publicada:
1 jun 2020
Ahead of Print:
1 may 2020
Resumen:
Protein venoms are effective cytotoxic molecules that when conveniently targeted to tumoral markers can be exploited as promising anticancer drugs. Here, it is explored whether the structurally unrelated melittin, gomesin, and CLIP71 could be functionally active when engineered, in form of GFP fusions, as self-assembling multimeric nanoparticles. Incorporated in modular constructs including a C-terminal polyhistidine tag and an N-terminal peptidic ligand of the cytokine receptor CXCR4 (overexpressed in more than 20 human neoplasias), these venoms are well produced in recombinant bacteria as proteolytically stable regular nanoparticles ranging between 12 and 35 nm. Being highly fluorescent, these materials selectively penetrate, label, and kill CXCR4(+) tumor cells in a CXCR4-dependent fashion. The obtained data support the concept of recombinant venoms as promising drugs, through the precise formulation as tumor-targeted nanomaterials for selective theragnostic applications in CXCR4(+) cancers.
Filiaciones:
Serna, N:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingenierfa Biomat & Nanomed CIBER BBN, Madrid 28029, Spain
Cano-Garrido, O:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingenierfa Biomat & Nanomed CIBER BBN, Madrid 28029, Spain
Univ Autonoma Barcelona, Nanoligent SL Edif Eureka, Barcelona 08193, Spain
Sanchez-Garcia, L:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingenierfa Biomat & Nanomed CIBER BBN, Madrid 28029, Spain
Pesarrodona, M:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingenierfa Biomat & Nanomed CIBER BBN, Madrid 28029, Spain
Barcelona Inst Sci & Technol, Inst Res Biomed IRB Barcelona, Barcelona 08028, Spain
Unzueta, U:
CIBER Bioingenierfa Biomat & Nanomed CIBER BBN, Madrid 28029, Spain
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, Barcelona 08041, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, Barcelona 08041, Spain
Sanchez-Chardi, A:
Univ Autonoma Barcelona, Serv Microscopia, Barcelona 08193, Spain
Univ Barcelona, Dept Biol Evolut Ecol & Cienscies Ambientals, Av Diagonal 643, Barcelona 08028, Spain
Mangues, R:
CIBER Bioingenierfa Biomat & Nanomed CIBER BBN, Madrid 28029, Spain
Hosp Santa Creu & Sant Pau, Biomed Res Inst St Pau IIB St Pau, Barcelona 08041, Spain
Hosp Santa Creu & Sant Pau, Josep Carreras Res Inst, Barcelona 08041, Spain
Vazquez, E:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingenierfa Biomat & Nanomed CIBER BBN, Madrid 28029, Spain
Villaverde, A:
Univ Autonoma Barcelona, Inst Biotecnol & Biomed, Barcelona 08193, Spain
Univ Autonoma Barcelona, Dept Genet & Microbiol, Barcelona 08193, Spain
CIBER Bioingenierfa Biomat & Nanomed CIBER BBN, Madrid 28029, Spain
Green Accepted
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