Department of Chemistry, Rice University, Houston, TX 77005.
Department of Electrical and Computer Engineering, Rice University, Houston, TX 77005.
Proc Natl Acad Sci U S A. 2017 Nov 21;114(47):12419-12424. doi: 10.1073/pnas.1713137114. Epub 2017 Nov 6.
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 (SiO 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.
远程控制、局部药物输送对于通过常规手段给药时潜在地最小化典型疏水性化疗药物引起的全身毒性是非常理想的。基于纳米粒子的药物输送系统为局部药物输送提供了一种很有前途的方法，是癌症治疗中一个新兴的研究领域。在这里，我们展示了两种药物分子从 DNA 基和蛋白质基宿主的近红外光触发释放，这两种宿主都被共轭到近红外吸收的 Au 纳米壳（SiO 核，Au 壳）上，每个都形成一个光响应药物输送复合物。我们表明，取决于药物分子、宿主分子的类型和激光照射方法（连续波或脉冲激光），这两种基于纳米粒子的复合物都可以实现体外光触发释放。两种乳腺癌药物，多西他赛和 HER2 靶向的拉帕替尼，被递送到 MDA-MB-231 和 SKBR3（HER2 过表达）乳腺癌细胞，并与非癌细胞 RAW 264.7 巨噬细胞中的释放进行了比较。连续波激光诱导基于纳米壳的 DNA 主链复合物中多西他赛的释放导致细胞死亡增加，这也与光热加热引起的非特异性细胞死亡一致。使用飞秒脉冲激光，基于纳米壳的人血清白蛋白蛋白主链复合物中拉帕替尼的释放导致癌细胞死亡增加，而正常细胞不受影响。这两种方法都提供了空间和时间上的局部药物释放策略，可以在特定的治疗部位和特定的时间窗口内提供高浓度的化疗药物，从而极大地减少副作用。
