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Glycine N ‐Methylation in NGR‐Tagged Nanocarriers Prevents Isoaspartate Formation and Integrin Binding without Impairing CD13 Recognition and Tumor Homing

2017; Wiley; Volume: 27; Issue: 36 Linguagem: Inglês

10.1002/adfm.201701245

1616-3028

Angelo Corti, Anna Maria Gasparri, Michela Ghitti, Angelina Sacchi, Francesco Sudati, Martina Fiocchi, Valentina Buttiglione, Laura Perani, Alessandro Gori, Silvia Valtorta, Rosa Maria Moresco, Fabio Pastorino, Mirco Ponzoni, Giovanna Musco, Flavio Curnis,

Neuropeptides and Animal Physiology

NGR (asparagine-glycine-arginine) is a tumor vasculature-homing peptide motif widely used for the functionalization of drugs, nanomaterials and imaging compounds for cancer treatment and diagnosis. Unfortunately, this motif has a strong propensity to undergo rapid deamidation. This reaction, which converts NGR into isoDGR, is associated with receptor switching from CD13 to integrins, with potentially important manufacturing, pharmacological and toxicological implications. It is found that glycine N-methylation of NGR-tagged nanocarriers completely prevents asparagine deamidation without impairing CD13 recognition. Studies in animal models have shown that the methylated NGR motif can be exploited for delivering radiolabeled compounds and nanocarriers, such as tumor necrosis factor-α (TNF)-bearing nanogold and liposomal doxorubicin, to tumors with improved selectivity. These findings suggest that this NGR derivative is a stable and efficient tumor-homing ligand that can be used for delivering functional nanomaterials to tumor vasculature.