Oxaliplatin is a platinum-based drug used in clinic for cancer chemotherapy. Despite of its success, the non-selective effect on normal cells causes severe side-effects and hampers its applications. Targeted delivery of oxaliplatin to cancer cells is an effective approach to enhance drug efficacy and reduce adverse effect. In this work, the Pt(IV) prodrug of oxaliplatin has been conjugated to poly(ethylene glycol) (PEG) modified nanobody in order to achieve tumor targeting as well as improved circulation in vivo. The Pt(IV) prodrug was site-specifically linked to an anti-epidermal growth factor receptor (EGFR) nanobody, so that the drug can be accumulated more pronounced in EGFR positive tumor cells than in normal cells. The effect of different length of PEG on the drug circulation has been investigated, while the fusion of anti-albumin nanobody was used for comparison. The result demonstrates that the prolonged drug circulation significantly increases the in vivo drug efficiency of the oxaliplatin-nanobody conjugate.

奥沙利铂是临床上用于癌症化疗的铂类药物。尽管取得了成功，但对正常细胞的非选择性作用会导致严重的副作用并阻碍其应用。将奥沙利铂靶向递送至癌细胞是提高药物疗效和减少不良反应的有效途径。在这项工作中，奥沙利铂的 Pt(IV) 前药已与聚乙二醇 (PEG) 修饰的纳米体偶联，以实现肿瘤靶向以及改善体内循环. Pt(IV) 前药与抗表皮生长因子受体 (EGFR) 纳米体进行位点特异性连接，因此药物在 EGFR 阳性肿瘤细胞中的积累比在正常细胞中更明显。研究了不同长度的PEG对药物循环的影响，并以抗白蛋白纳米抗体的融合作为对比。结果表明，延长的药物循环显着提高了奥沙利铂-纳米抗体缀合物的体内药物效率。