Near-infrared remotely triggered drug-release strategies for cancer treatment
Near-infrared remotely triggered drug-release strategies for cancer treatment
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DOI：
10.1073/pnas.1713137114
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发表时间：
2017-11-21
影响因子：
11.1
通讯作者：
Halas, Naomi J.
中科院分区：
文献类型：
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作者：
Goodman, Amanda M.;Neumann, Oara;Halas, Naomi J.
远程控制、局部给药是非常可取的，因为可以潜在地最大限度地减少通过传统方法给药典型的疏水性化疗药物所引起的全身毒性。基于纳米颗粒的药物传递系统为局部药物传递提供了一种非常有前途的方法，是癌症治疗中的一个新兴领域。在这里，我们展示了两个药物分子在近红外光触发下从基于DNA和基于蛋白质的主体中释放出来，这两个分子已经连接到近红外吸收的Au纳米壳(SiO_2核，Au壳)，每个都形成了光响应性药物传递络合物。我们发现，根据药物分子、宿主分子的类型和激光照射方法(连续波或脉冲激光)，这两种类型的纳米颗粒络合物都可以在体外实现光触发释放。两种乳腺癌药物，多西紫杉醇和hER2靶向的拉帕替尼，被传递给mda-MB-231和SKBR3(高表达her2)乳腺癌细胞，并与非癌症RAW 264.7巨噬细胞的释放进行比较。连续波激光诱导多西紫杉醇从基于纳米壳的DNA宿主复合体中释放，显示细胞死亡增加，这也与光热加热引起的非特异性细胞死亡相一致。使用飞秒脉冲激光，拉帕替尼从基于纳米壳的人血清白蛋白宿主复合体中释放出来，导致癌细胞死亡增加，而非癌症对照细胞不受影响。这两种方法都提供了空间和时间上的局部药物释放策略，可以促进在特定治疗地点在特定时间窗口内提供高浓度的局部化疗药物，并有可能极大地减少副作用。
Remotely controlled, localized drug delivery is highly desirable for potentially minimizing the systemic toxicity induced by the administration of typically hydrophobic chemotherapy drugs by conventional means. Nanoparticle-based drug delivery systems provide a highly promising approach for localized drug delivery, and are an emerging field of interest in cancer treatment. Here, we demonstrate near-IR light-triggered release of two drug molecules from both DNA-based and protein-based hosts that have been conjugated to near-infrared-absorbing Au nanoshells (SiO2 core, Au shell), each forming a light-responsive drug delivery complex. We show that, depending upon the drug molecule, the type of host molecule, and the laser illumination method (continuous wave or pulsed laser), in vitro light-triggered release can be achieved with both types of nanoparticle-based complexes. Two breast cancer drugs, docetaxel and HER2-targeted lapatinib, were delivered to MDA-MB-231 and SKBR3 (overexpressing HER2) breast cancer cells and compared with release in noncancerous RAW 264.7 macrophage cells. Continuous wave laser-induced release of docetaxel from a nanoshell-based DNA host complex showed increased cell death, which also coincided with nonspecific cell death from photothermal heating. Using a femtosecond pulsed laser, lapatinib release from a nanoshell-based human serum albumin protein host complex resulted in increased cancerous cell death while noncancerous control cells were unaffected. Both methods provide spatially and temporally localized drug-release strategies that can facilitate high local concentrations of chemotherapy drugs deliverable at a specific treatment site over a specific time window, with the potential for greatly minimized side effects.