Aminopeptidase N(APN)/CD13 is a transmembrane glycoprotein,which is overexpressed on tumor neovascular endothelial cells and most tumor cells,where it plays an important role in tumor angiogenesis.Peptides containing ...Aminopeptidase N(APN)/CD13 is a transmembrane glycoprotein,which is overexpressed on tumor neovascular endothelial cells and most tumor cells,where it plays an important role in tumor angiogenesis.Peptides containing the Asn-Gly-Arg(NGR)motif can specifically recognize APN/CD13 allowing them to act as tumor-homing peptides for the targeted delivery of anti-tumor drugs to tumor neovascular endothelial cells and tumor cells.This article reviews the literature and recent developments related to APN/CD13,its role in tumor growth and some antitumor drug delivery systems containing NGR peptides designed to target APN/CD13.展开更多
Previously developed Asn-Gly-Arg(NGR) peptide-modified multifunctional poly(ethyleneimine)–poly(ethylene glycol)(PEI–PEG)-based nanoparticles(TPIC) have been considered to be promising carriers for the co-delivery o...Previously developed Asn-Gly-Arg(NGR) peptide-modified multifunctional poly(ethyleneimine)–poly(ethylene glycol)(PEI–PEG)-based nanoparticles(TPIC) have been considered to be promising carriers for the co-delivery of DNA and doxorubicin(DOX). As a continued effort, the aim of the present study was to further evaluate the interaction between TPIC and human umbilical vein endothelial cells(HUVEC) to better understand the cellular entry mechanism. In the present investigation,experiments relevant to co-localization, endocytosis inhibitors and factors influencing the internalization were performed. Without any treatment, there was no co-localization between aminopeptidase N/CD13(APN/CD13) and caveolin 1(CAV1). However, co-localization between CD13 and CAV1 was observed when cells were incubated with an anti-CD13 antibody or TPIC. As compared with antibody treatment,TPIC accelerated the speed and enhanced the degree of co-localization. TPIC entered HUVEC not only together with CD13 but also together with CAV1. However, this internalization was not dependent on the enzyme activity of CD13 but could be inhibited by methyl-β-eyclodextfin(MβCD), further identifying the involvement of caveolae-mediated endocytosis(CvME). This conclusion was also verified by endocytosis inhibitor experiments.展开更多
基金This research was supported by the National Basic Research Program of China(No.2009CB930300)State Key Projects(No.2009ZX09310-001)the 863 Project(No.2007AA021811).
文摘Aminopeptidase N(APN)/CD13 is a transmembrane glycoprotein,which is overexpressed on tumor neovascular endothelial cells and most tumor cells,where it plays an important role in tumor angiogenesis.Peptides containing the Asn-Gly-Arg(NGR)motif can specifically recognize APN/CD13 allowing them to act as tumor-homing peptides for the targeted delivery of anti-tumor drugs to tumor neovascular endothelial cells and tumor cells.This article reviews the literature and recent developments related to APN/CD13,its role in tumor growth and some antitumor drug delivery systems containing NGR peptides designed to target APN/CD13.
基金supported by the National Natural Science Foundation(No.81402867)
文摘Previously developed Asn-Gly-Arg(NGR) peptide-modified multifunctional poly(ethyleneimine)–poly(ethylene glycol)(PEI–PEG)-based nanoparticles(TPIC) have been considered to be promising carriers for the co-delivery of DNA and doxorubicin(DOX). As a continued effort, the aim of the present study was to further evaluate the interaction between TPIC and human umbilical vein endothelial cells(HUVEC) to better understand the cellular entry mechanism. In the present investigation,experiments relevant to co-localization, endocytosis inhibitors and factors influencing the internalization were performed. Without any treatment, there was no co-localization between aminopeptidase N/CD13(APN/CD13) and caveolin 1(CAV1). However, co-localization between CD13 and CAV1 was observed when cells were incubated with an anti-CD13 antibody or TPIC. As compared with antibody treatment,TPIC accelerated the speed and enhanced the degree of co-localization. TPIC entered HUVEC not only together with CD13 but also together with CAV1. However, this internalization was not dependent on the enzyme activity of CD13 but could be inhibited by methyl-β-eyclodextfin(MβCD), further identifying the involvement of caveolae-mediated endocytosis(CvME). This conclusion was also verified by endocytosis inhibitor experiments.
