Nanogold Functionalized With Lipoamide-isoDGR: A Simple, Robust and Versatile Nanosystem for αvβ3-Integrin Targeting
Articolo
Data di Pubblicazione:
2021
Citazione:
Nanogold Functionalized With Lipoamide-isoDGR: A Simple, Robust and Versatile Nanosystem for αvβ3-Integrin Targeting / A. Sacchi, A.M. Gasparri, M. Monieri, G. Anderluzzi, B. Colombo, A. Gori, A. Corti, F. Curnis. - In: FRONTIERS IN CHEMISTRY. - ISSN 2296-2646. - 9:(2021 May 28), pp. 690357.1-690357.11. [10.3389/fchem.2021.690357]
Abstract:
Gold nanoparticles functionalized with isoDGR, a tripeptide motif that recognizes alpha v beta 3 integrin overexpressed in tumor vessels, have been used as nano-vectors for the delivery of cytokines to tumors. Functionalization of nanogold with this peptide has been achieved by coating nanoparticles with a peptide-albumin conjugate consisting of heterogeneous molecules with a variable number of linkers and peptides. To reduce nanodrug heterogeneity we have designed, produced and preclinically evaluated a homogeneous and well-defined reagent for nanogold functionalization, consisting of a head-to-tail cyclized CGisoDGRG peptide (iso1) coupled via its thiol group to maleimide-PEG(11)-lipoamide (LPA). The resulting iso1-PEG(11)-LPA compound can react with nanogold via lipoamide to form a stable bond. In vitro studies have shown that iso1, after coupling to nanogold, maintains its capability to bind purified alpha v beta 3 and alpha v beta 3-expressing cells. Nanogold functionalized with this peptide can also be loaded with bioactive tumor necrosis factor-alpha (TNF) to form a bi-functional nanodrug that can be stored for three days at 37 degrees C or >1 year at low temperatures with no loss alpha v beta 3-binding properties and TNF-cytolytic activity. Nanoparticles functionalized with both iso1 and TNF induced tumor eradication in WEHI-164 fibrosarcoma-bearing mice more efficiently than nanoparticles lacking the iso1 targeting moiety. These results suggest that iso1-PEG(11)-LPA is an efficient and well-defined reagent that can be used to produce robust and more homogeneous nano-vectors for the delivery of TNF and other cytokines to alpha v beta 3 positive cells.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
TNF; gold nanoparticles; isoAsp-Gly-Arg (isoDGR); lipoamide; polyethylene glycol; tumor vascular targeting; αvβ3 integrin
Elenco autori:
A. Sacchi, A.M. Gasparri, M. Monieri, G. Anderluzzi, B. Colombo, A. Gori, A. Corti, F. Curnis
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