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

作　　者：Flavio Curnis Martina Fiocch Angelina Sacchi Alessandro Gori Anna Gasparri Angelo Corti 

机构地区：[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]Vita Salute San Raffaele University, Milan 20132, Italy

出　　处：《Nano Research》2016年第5期1393-1408,共16页纳米研究（英文版）

摘　　要：Colloidal gold （Au）, a well-tolerated several applications in nanomedicine. nanomaterial, is currently exploited for 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 scaffoldflinker used for gold functionalization is critical for CD13 recognition. Using fibrosarcorna-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.Colloidal gold （Au）, a well-tolerated several applications in nanomedicine. nanomaterial, is currently exploited for 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 scaffoldflinker used for gold functionalization is critical for CD13 recognition. Using fibrosarcorna-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.

关 键 词：Asn-Gly-Arg （NGR） isoAsp-Gly-Arg （isoDGR） CD13 INTEGRIN tumor necrosis factor albumin gold nanoparticles 

分 类 号：Q279[生物学—细胞生物学] TP212.3[自动化与计算机技术—检测技术与自动化装置]