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Engineering Protein Venoms as Self‐Assembling CXCR4‐Targeted Cytotoxic Nanoparticles
Author(s) -
Serroa,
CanoGarrido Olivia,
SánchezGarcía Laura,
Pesarrodona Mireia,
Unzueta Ugutz,
SánchezChardi Alejandro,
Mangues Ramon,
Vázquez Esther,
Villaverde Antonio
Publication year - 2020
Publication title -
particle and particle systems characterization
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.877
H-Index - 56
eISSN - 1521-4117
pISSN - 0934-0866
DOI - 10.1002/ppsc.202000040
Subject(s) - melittin , recombinant dna , chemistry , cytotoxic t cell , computational biology , nanotechnology , peptide , biochemistry , biology , in vitro , materials science , gene
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.