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 （...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.展开更多
In the present study, we prepared novel NGR-modified PEG-PLGA polymeric micelles containing paclitaxel （NGR- PM-PTX） in order to evaluate their potential targeting to aminopeptidase N receptors expressed on tumor en...In the present study, we prepared novel NGR-modified PEG-PLGA polymeric micelles containing paclitaxel （NGR- PM-PTX） in order to evaluate their potential targeting to aminopeptidase N receptors expressed on tumor endothelial cells and the tumor cell surface and its anti-tumor activity in vitro and in vivo. NGR-PM-PTX was prepared by thin-film hydration method. The in vitro targeting characteristics of NGR-modified PM on HUVEC （human umbilical vein endothelial cells）, HT1080 （human fibrosarcoma cells） and MCF-7 （human breast adenocarcinoma cells） were then investigated. The anti-tumor activity of NGR-PM-PTX was evaluated in HT1080 tumor-bearing mice in vivo. The targeting activity of the NGR-modified PM was demonstrated by flow cytometry and confocal microscopy in vitro. NGR-PM-PTX also produced marked anti-tumor activity to HTI080 tumor-beating mice in vivo.展开更多
文摘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.
基金National Natural Science Foundation of China (Grant No.30873170)
文摘In the present study, we prepared novel NGR-modified PEG-PLGA polymeric micelles containing paclitaxel （NGR- PM-PTX） in order to evaluate their potential targeting to aminopeptidase N receptors expressed on tumor endothelial cells and the tumor cell surface and its anti-tumor activity in vitro and in vivo. NGR-PM-PTX was prepared by thin-film hydration method. The in vitro targeting characteristics of NGR-modified PM on HUVEC （human umbilical vein endothelial cells）, HT1080 （human fibrosarcoma cells） and MCF-7 （human breast adenocarcinoma cells） were then investigated. The anti-tumor activity of NGR-PM-PTX was evaluated in HT1080 tumor-bearing mice in vivo. The targeting activity of the NGR-modified PM was demonstrated by flow cytometry and confocal microscopy in vitro. NGR-PM-PTX also produced marked anti-tumor activity to HTI080 tumor-beating mice in vivo.
