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Noncovalent functionalization of carbon nanovectors with an antibody enables targeted drug delivery

机译:碳纳米载体与抗体的非共价功能化可实现靶向药物递送

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Current chemotherapeutics are characterized by efficient tumor cell-killing and severe side effects mostly derived from off-target toxicity. Hence targeted delivery of these drugs to tumor cells is actively sought. We previously demonstrated that poly(ethylene glycol)-functionalized carbon nanovectors are able to sequester paclitaxel, a widely used hydrophobic cancer drug, by simple physisorption and thereby deliver the drug for killing of cancer cells. The cell-killing when these drug-loaded carbon nanoparticles were used was equivalent to when a commercial formulation of paclitaxel was used. Here we show that by further mixing the drug-loaded nanoparticles with Cetuximab, a monoclonal antibody that recognizes the epidermal growth factor receptor (EGFR), paclitaxel is preferentially targeted to EGFR+ tumor cells in vitro. This supports progressing to in vivo studies. Moreover, the construct is unusual in that all three components are assembled through noncovalent interactions. Such noncovalent assembly could enable high-throughput screening of drug/antibody combinations.
机译:当前的化学疗法的特征在于有效的肿瘤细胞杀伤和严重的副作用,这些副作用主要来自脱靶毒性。因此,积极寻求将这些药物靶向递送至肿瘤细胞。我们先前证明,聚乙二醇功能化的碳纳米载体能够通过简单的物理吸附作用来隔离紫杉醇(紫杉醇),紫杉醇是一种广泛使用的疏水性癌症药物,从而能够将其用于杀死癌细胞。当使用这些载有药物的碳纳米颗粒时,细胞杀灭作用与使用紫杉醇的商业制剂时的杀灭作用相同。在这里,我们显示通过将载药的纳米颗粒与西妥昔单抗(一种识别表皮生长因子受体(EGFR)的单克隆抗体)进一步混合,紫杉醇在体外优先靶向EGFR +肿瘤细胞。这支持了进行体内研究。而且,该构造是不寻常的,因为所有三个组分都是通过非共价相互作用组装的。这种非共价组装可以实现药物/抗体组合的高通量筛选。

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