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Curnis F, Fiocchi M, Sacchi A, et al. NGR-tagged nano-gold: A new CD13-selective carrier for cytokine delivery to tumors. Nano Res. 2016;9(5):1393-1408doi: 10.1007/s12274-016-1035-8.
Curnis, F., Fiocchi, M., Sacchi, A., Gori, A., Gasparri, A., & Corti, A. (2016). NGR-tagged nano-gold: A new CD13-selective carrier for cytokine delivery to tumors. Nano research, 9(5), 1393-1408. https://doi.org/10.1007/s12274-016-1035-8
Curnis, Flavio, et al. "NGR-tagged nano-gold: A new CD13-selective carrier for cytokine delivery to tumors." Nano research vol. 9,5 (2016): 1393-1408. doi: https://doi.org/10.1007/s12274-016-1035-8
Curnis F, Fiocchi M, Sacchi A, Gori A, Gasparri A, Corti A. NGR-tagged nano-gold: A new CD13-selective carrier for cytokine delivery to tumors. Nano Res. 2016 May;9(5):1393-1408. doi: 10.1007/s12274-016-1035-8. Epub 2016 Mar 04. PMID: 27226823; PMCID: PMC4876925.
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Nano Res. 2016 May;9(5):1393-1408. doi: 10.1007/s12274-016-1035-8. Epub 2016 Mar 04.

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

Nano research

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

Affiliations

  1. Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy.
  2. Istituto di Chimica del Riconoscimento Molecolare, CNR, Milan 20131, Italy.
  3. Division of Experimental Oncology, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy; Vita Salute San Raffaele University, 20132, Milan.

PMID: 27226823 PMCID: PMC4876925 DOI: 10.1007/s12274-016-1035-8

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.

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

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