The dynamic or flowing tumor cells just as leukemia cells and circulating tumor cells face a microenvironment difference from the solid tumors, and the related targeting nanomedicines are rarely reported. The existence of fluidic shear stress in blood circulation seems not favorable for the binding of ligand modified nanodrugs with their target receptor. Namely, the binding feature is very essential in this case. Herein, we utilized HSPC, PEG-DSPE, cholesterol and two αvβ3 ligands (RGDm7 and DT4) with different binding rates to build dual-targeting nanovesicles, in an effort to achieve a “fast-binding/slow-unbinding” function. It was demonstrated that the dual-targeting nanovesicles actualized efficient cellular uptake and antitumor effect in vitro both for static and dynamic tumor cells. Besides, the potency of the dual-targeting vesicles for flowing tumor cells was better than that for static tumor cells. Then, a tumor metastasis mice model and a leukemia mice model were established to detect the killing ability of the drug-loaded dual-targeting vesicles to dynamic tumor cells in vivo. The therapy efficacy of the dual-targeting system was higher than other controls including single-targeting ones. Generally, it seems possible to strengthen drug-targeting to dynamic tumor cells via the control of ligand–receptor interaction.

就像白血病细胞和循环肿瘤细胞一样，动态或流动的肿瘤细胞与实体瘤也面临着微环境的差异，很少报道相关的靶向纳米药物。血液循环中流体剪切应力的存在似乎不利于配体修饰的纳米药物与其靶受体的结合。即，在这种情况下，绑定功能非常重要。在此，我们使用HSPC，PEG-DSPE，胆固醇和两个α v β 3点的配体（RGDm7和DT4）具有不同结合速率来构建双重靶向纳米囊泡，以努力实现了“快速结合/慢解绑定”功能。结果表明，双重靶向纳米囊泡在体外可实现有效的细胞摄取和抗肿瘤作用对于静态和动态肿瘤细胞。此外，双靶囊泡对流动肿瘤细胞的效力要优于对静态肿瘤细胞的效力。然后，建立肿瘤转移小鼠模型和白血病小鼠模型以检测载药的双重靶向囊泡对体内动态肿瘤细胞的杀伤能力。双靶向系统的治疗效果高于其他对照，包括单靶向系统。通常，似乎可以通过控制配体-受体相互作用来加强针对动态肿瘤细胞的药物靶向。