Engineering Protein Venoms as Self-Assembling CXCR4-Targeted Cytotoxic Nanoparticles

Naroa Serna, Olivia Cano-Garrido, Laura Sánchez-García, Mireia Pesarrodona, Ugutz Unzueta, Alejandro Sánchez-Chardi, Ramon Mangues, Esther Vázquez*, Antonio Villaverde

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number2000040
JournalParticle and Particle Systems Characterization
Volume37
Issue number6
DOIs
Publication statusPublished - 1 Jun 2020

Keywords

  • cytotoxic nanoparticles
  • functional materials
  • protein venoms
  • self-assembled nanoparticles

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