Abstract
Abstract Colloidal gold (Au) is a well-tolerated nanomaterial currently exploited for several applications in the field of nanomedicine. In particular, gold nanoparticles loaded with tumor necrosis factor-alpha (TNF), a cytokine endowed with anti tumor activity, have a therapeutic index higher than that of TNF. For this reason TNF-gold nanoparticles are currently tested in cancer patients. We have addressed the hypothesis that TNF-gold nanoparticles tagged with tumor vasculature homing peptides have improved therapeutic properties. To this aim we have tagged TNF-gold nanoparticles with albumin-peptide conjugates containing the NGR (Asn-Gly-Arg) or isoDGR (isoAsp-Gly-Arg) motives, i.e. with ligands of CD13 and integrin alphavbeta3, respectively, expressed by the tumor neovasculature. The therapeutic properties of the resulting nanodrugs (called NGR-HSA/Au/TNF and isoDGR-HSA/Au/TNF) were then investigated in fibrosarcoma- or lymphoma-bearing mice and compared with those a nanodrug lacking the targeting peptide (called HSA/Au/TNF). The results showed that intravenous administration of extremely low doses of NGR-HSA/Au/TNF or isoDGR-HSA/Au/TNF (equivalent to 5 pg of bioactive TNF/mouse) were sufficient to induce anti-tumor effects, whereas similar doses of HSA/Au/TNF were minimally active. Low-dose NGR-HSA/Au/TNF and isoDGR-HSA/Au/TNF, but not HSA/Au/TNF, could also exert synergistic anti-tumor effects with melphalan, a chemotherapeutic drug. These findings support the concept that tagging TNF-gold nanoparticles with tumor vasculature homing peptides have an improved antitumor activity, likely because of an active targeting mechanism. Citation Format: Flavio Curnis, AnnaMaria Gasparri, Angelina Sacchi, Martina Fiocchi, Angelo Corti. Anti-tumor activity of TNF-gold nanodrugs tagged with tumor vasculature-homing peptides containing the NGR or isoDGR motives. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4387. doi:10.1158/1538-7445.AM2015-4387
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