NGR-tagged nano-gold: A new CD13-selective carrier for cytokine delivery to tumors

Flavio Curnis, Martina Fiocchi, Angelina Sacchi, Alessandro Gori, Anna Gasparri, Angelo Corti

Research output: Contribution to journalArticle

Abstract

Colloidal gold (Au), a well-tolerated nanomaterial, is currently exploited for several applications in nanomedicine. We show that gold nanoparticles tagged with a novel tumor-homing peptide containing Asn-Gly-Arg (NGR), a ligand of CD13 expressed by the tumor neovasculature, can be exploited as carriers for cytokine delivery to tumors. Biochemical and functional studies showed that the NGR molecular scaffold/linker used for gold functionalization is critical for CD13 recognition. Using fibrosarcoma-bearing mice, NGR-tagged nanodrugs could deliver extremely low, yet pharmacologically active doses of tumor necrosis factor (TNF), an anticancer cytokine, to tumors with no evidence of toxicity. Mechanistic studies confirmed that CD13 targeting was a primary mechanism of drug delivery and excluded a major role of integrin targeting consequent to NGR deamidation, a degradation reaction that generates the isoAsp-Gly-Arg (isoDGR) integrin ligand. NGR-tagged gold nanoparticles can be used, in principle, as a novel platform for single- or multi-cytokine delivery to tumor endothelial cells for cancer therapy. [Figure not available: see fulltext.]
Original languageEnglish
Pages (from-to)1393 - 1408
Number of pages16
JournalNano Research
Volume9
Issue number5
DOIs
Publication statusPublished - May 1 2016

Fingerprint

Gold
Tumors
Cytokines
Integrins
Bearings (structural)
Ligands
Nanoparticles
Medical nanotechnology
Gold Colloid
Endothelial cells
Drug delivery
Nanostructured materials
Scaffolds
Peptides
Toxicity
Tumor Necrosis Factor-alpha
Degradation

Keywords

  • albumin
  • Asn-Gly-Arg (NGR)
  • CD13
  • gold nanoparticles
  • integrin
  • isoAsp-Gly-Arg (isoDGR)
  • tumor necrosis factor

ASJC Scopus subject areas

  • Electrical and Electronic Engineering
  • Materials Science(all)

Cite this

NGR-tagged nano-gold: A new CD13-selective carrier for cytokine delivery to tumors. / Curnis, Flavio; Fiocchi, Martina; Sacchi, Angelina; Gori, Alessandro; Gasparri, Anna; Corti, Angelo.

In: Nano Research, Vol. 9, No. 5, 01.05.2016, p. 1393 - 1408.

Research output: Contribution to journalArticle

Curnis, Flavio ; Fiocchi, Martina ; Sacchi, Angelina ; Gori, Alessandro ; Gasparri, Anna ; Corti, Angelo. / NGR-tagged nano-gold: A new CD13-selective carrier for cytokine delivery to tumors. In: Nano Research. 2016 ; Vol. 9, No. 5. pp. 1393 - 1408.
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