Programmed Nanoparticle-Loaded Nanoparticles for Deep-Penetrating 3D Cancer Therapy
Programmed Nanoparticle-Loaded Nanoparticles for Deep-Penetrating 3D Cancer Therapy
复制标题
可编程纳米粒子负载纳米粒子用于深穿透三维癌症治疗
DOI：
10.1002/adma.201707557
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发表时间：
2018-07-19
影响因子：
29.4
通讯作者：
Kim, Won Jong
中科院分区：
文献类型：
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作者：
Kim, Jinhwan;Jo, Changshin;Kim, Won Jong
肿瘤是 3D 的，由细胞团块和血管组成。由于血管结构渗漏，涉及纳米粒子的疗法利用特定的积累。然而，全身注射的纳米粒子大多被位于癌症组织表面的细胞摄取，缺乏深入渗透到核心癌症区域的能力。在此，报道了一种前所未有的策略，即注射纳米颗粒负载的纳米颗粒来解决长期存在的问题，以在整个 3D 肿瘤中有效地从表面到核心进行药物输送。负载纳米粒子的纳米粒子是二氧化硅纳米粒子（约150 nm），具有发达的互连通道（直径约30 nm），其中包含具有可编程DNA的小金纳米粒子（AuNP）（约15 nm）。负载纳米颗粒（AuNPs）的纳米颗粒（二氧化硅）：（1）通过在血液循环过程中保护内部治疗性AuNPs，可以通过渗漏的血管结构在肿瘤中积累，然后（2）允许AuNPs扩散渗透到整个表面到核心的肿瘤组织中，最后（3）通过癌症特征的pH梯度触发释放药物。分层纳米颗粒负载的纳米颗粒可以成为癌症治疗的合理设计，因为外部的大纳米颗粒可有效促进血液循环并保护内部的治疗性纳米颗粒，从而使负载的小纳米颗粒能够深入渗透到抗癌药物的3D肿瘤中。
Tumors are 3D, composed of cellular agglomerations and blood vessels. Therapies involving nanoparticles utilize specific accumulations due to the leaky vascular structures. However, systemically injected nanoparticles are mostly uptaken by cells located on the surfaces of cancer tissues, lacking deep penetration into the core cancer regions. Herein, an unprecedented strategy, described as injecting nanoparticle-loaded nanoparticles to address the long-lasting problem is reported for effective surface-to-core drug delivery in entire 3D tumors. The nanoparticle-loaded nanoparticle is a silica nanoparticle (approximate to 150 nm) with well-developed, interconnected channels (diameter of approximate to 30 nm), in which small gold nanoparticles (AuNPs) (approximate to 15 nm) with programmable DNA are located. The nanoparticle (AuNPs)-loaded nanoparticles (silica): (1) can accumulate in tumors through leaky vascular structures by protecting the inner therapeutic AuNPs during blood circulation, and then (2) allow diffusion of the AuNPs for penetration into the entire surface-to-core tumor tissues, and finally (3) release a drug triggered by cancer-characteristic pH gradients. The hierarchical nanoparticle-loaded nanoparticle can be a rational design for cancer therapies because the outer large nanoparticles are effective in blood circulation and in protection of the therapeutic nanoparticles inside, allowing the loaded small nanoparticles to penetrate deeply into 3D tumors with anticancer drugs.