Corti Angelo, Gasparri Anna Maria, Ghitti Michela, Sacchi Angelina, Sudati Francesco, Fiocchi Martina, Buttiglione Valentina, Perani Laura, Gori Alessandro, Valtorta Silvia, Moresco Rosa Maria, Pastorino Fabio, Ponzoni Mirco, Musco Giovanna, Curnis Flavio
IRCCS San Raffaele Scientific Institute and Vita Salute San Raffaele University, Milan, 20132, Italy.
IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132, Milan, Italy.
Adv Funct Mater. 2017 Sep 26;27(36). doi: 10.1002/adfm.201701245.
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 DGR, is associated with receptor switching from CD13 to integrins, with potentially important manufacturing, pharmacological and toxicological implications. It is found that glycine -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.
NGR（天冬酰胺-甘氨酸-精氨酸）是一种肿瘤血管靶向肽基序，广泛用于药物、纳米材料和成像化合物的功能化，以用于癌症治疗和诊断。不幸的是，该基序极易发生快速脱酰胺反应。此反应将NGR转化为DGR，与受体从CD13转换为整合素有关，具有潜在重要的生产、药理学和毒理学意义。研究发现，NGR标记的纳米载体的甘氨酸甲基化可完全防止天冬酰胺脱酰胺，而不会损害CD13识别。动物模型研究表明，甲基化的NGR基序可用于将放射性标记化合物和纳米载体，如携带肿瘤坏死因子-α（TNF）的纳米金和脂质体阿霉素，以更高的选择性递送至肿瘤。这些发现表明，这种NGR衍生物是一种稳定且高效的肿瘤靶向配体，可用于将功能性纳米材料递送至肿瘤血管。
