School of Molecular Sciences , University of Western Australia , 35 Stirling Highway , Crawley , Western Australia Australia , 6009.
CSIRO Manufacturing , New Horizons Centre , 20 Research Way , Clayton , Victoria Australia 3168.
Langmuir. 2018 Dec 18;34(50):15343-15349. doi: 10.1021/acs.langmuir.8b02946. Epub 2018 Nov 27.
The role of nanoparticles in cancer medicine is vast with debate still surrounding the distinction between therapeutic efficacy of actively targeted nanoparticles versus passively targeted systems for drug delivery. While it is commonly accepted that methodologies that result in homing a high concentration of drug loaded nanoparticles to the tumor is beneficial, the role of intracellular trafficking of these nanoparticles in dictating the overall therapeutic outcome remains unresolved. Herein we demonstrate that the therapeutic outcome of drug loaded nanoparticles is governed beyond simply enabling nanoparticle internalization in cells. Using two model polymeric nanoparticles, one decorated with the GE11 peptide for active targeting of the epidermal growth factor receptor (EGFR) and the other without, we demonstrate that EGFR mediated intracellular internalization results in an enhanced therapeutic effect compared to the nontargeted formulation. Our findings demonstrate that the intracellular destination of nanoparticles beyond its ability to internalize is an important parameter that has to be accounted for in the design of targeted drug delivery systems.
纳米颗粒在癌症医学中的作用是广泛的，目前仍围绕着主动靶向纳米颗粒的治疗效果与被动靶向药物传递系统之间的区别展开争论。虽然人们普遍认为，使载药纳米颗粒高度集中到肿瘤部位的方法是有益的，但这些纳米颗粒在细胞内的运输方式对整体治疗效果的影响仍未得到解决。在此，我们证明了载药纳米颗粒的治疗效果不仅仅取决于使纳米颗粒在细胞内内化的能力。使用两种模型聚合物纳米颗粒，一种用 GE11 肽修饰以主动靶向表皮生长因子受体（EGFR），另一种没有修饰，我们证明了 EGFR 介导的细胞内内化与非靶向制剂相比，具有增强的治疗效果。我们的研究结果表明，纳米颗粒的细胞内归宿除了其内化能力之外，是靶向药物传递系统设计中必须考虑的一个重要参数。
