Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, USA.
ACS Nano. 2012 May 22;6(5):4157-68. doi: 10.1021/nn300652p. Epub 2012 Apr 13.
While nanoparticles maximize the amount of chemotherapeutic drug in tumors relative to normal tissues, nanoparticle-based drugs are not accessible to the majority of cancer cells because nanoparticles display patchy, near-perivascular accumulation in tumors. To overcome the limitations of current drugs in their molecular or nanoparticle form, we developed a nanoparticle based on multicomponent nanochains to deliver drug to the majority of cancer cells throughout a tumor while reducing off-target delivery. The nanoparticle is composed of three magnetic nanospheres and one doxorubicin-loaded liposome assembled in a 100 nm long chain. These nanoparticles display prolonged blood circulation and significant intratumoral deposition in tumor models in rodents. Furthermore, the magnetic particles of the chains serve as a mechanical transducer to transfer radio frequency energy to the drug-loaded liposome. The defects on the liposomal walls trigger the release of free drug capable of spreading throughout the entire tumor, which results in a widespread anticancer effect.
虽然纳米颗粒相对于正常组织而言能最大限度地增加肿瘤中的化疗药物含量,但由于纳米颗粒在肿瘤中呈斑片状、近乎血管周围的聚集,大多数癌细胞无法接触到基于纳米颗粒的药物。为了克服当前药物在分子或纳米颗粒形式上的局限性,我们开发了一种基于多组分纳米链的纳米颗粒,以将药物递送至肿瘤中的大多数癌细胞,同时减少非靶向递药。该纳米颗粒由三个磁性纳米球和一个载多柔比星的脂质体组成,组装成长度为 100nm 的链。这些纳米颗粒在啮齿动物肿瘤模型中表现出延长的血液循环和显著的肿瘤内沉积。此外,链条的磁性颗粒可用作机械换能器,将射频能量传递到载药脂质体。脂质体壁上的缺陷会触发游离药物的释放,这些游离药物能够扩散到整个肿瘤中,从而产生广泛的抗癌效果。