Although high-efficiency targeted delivery is investigated for years, the efficiency of tumor targeting seems still a hard core to smash. To overcome this problem, we design a three-step delivery strategy based on streptavidin–biotin interaction with the help of c(RGDfK), magnetic fields and lasers. The ultrasmall superparamagnetic iron oxide nanoparticles (USIONPs) modified with c(RGDfK) and biotin are delivered at step 1, followed by streptavidin and the doxorubicin (Dox) loaded nanosystems conjugated with biotin at steps 2 and 3, respectively. The delivery systems were proved to be efficient on A549 cells. The co-localization of signal for each step revealed the targeting mechanism. The external magnetic field could further amplify the endocytosis of USPIONs based on c(RGDfK), and magnify the uptake distinctions among different test groups. Based on photoacoustic imaging, laser-heating treatment could enhance the permeability of tumor venous blood vessels and change the insufficient blood flow in cancer. Then, it was noticed in vivo that only three-step delivery with laser-heating and magnetic fields realized the highest tumor distribution of nanosystem. Finally, the magnetism/laser-auxiliary cascaded delivery exhibited the best antitumor efficacy. Generally, this study demonstrated the necessity of combining physical, biological and chemical means of targeting.

尽管对高效靶向递送的研究已经进行了多年，但靶向肿瘤的效率似乎仍然难以突破。为了克服这个问题，我们在链霉抗生物素蛋白-生物素的作用下，借助c（RGDfK），磁场和激光，设计了一个三步传递策略。经过c（RGDfK）和生物素修饰的超小型超顺磁性氧化铁纳米粒子（USIONPs）在步骤1交付，然后分别在步骤2和3分别加载了链霉亲和素和与生物素缀合的阿霉素（Dox）纳米系统。递送系统被证明对A549细胞有效。每个步骤的信号共定位揭示了靶向机制。外部磁场可以进一步基于c（RGDfK）放大USPIONs的胞吞作用，并扩大不同测试组之间的摄取差异。基于光声成像，激光加热治疗可以增强肿瘤静脉血管的通透性，改变癌症中不足的血流。然后，它被注意到在体内，只有通过激光加热和磁场的三步传递才能实现纳米系统中肿瘤的最高分布。最后，磁性/激光辅助级联递送表现出最佳的抗肿瘤功效。一般而言，这项研究证明了结合物理，生物和化学靶向手段的必要性。