Yang Celina, Neshatian Mehrnoosh, van Prooijen Monique
J Nanosci Nanotechnol. 2014 Jul;14(7):4813-9. doi: 10.1166/jnn.2014.9280.
The applications of nanoparticles (NPs) for improved therapeutics are at the forefront of cancer nanotechnology. Gold nanoparticles (GNPs) have been extensively used due to their ability to act as both an anticancer drug carrier in chemotherapy and as a dose enhancer in radiotherapy. GNPs used in the studies were predominantly localized in the cell cytoplasm. However, the therapeutic response can be further enhanced if NPs can be effectively targeted into the nucleus. Here, we present an effective strategy for designing a GNP-peptide complex for nuclear targeting. Two peptides were conjugated onto a NP: One peptide enhanced the uptake while the other peptide enhanced the nuclear delivery. The nuclear targeted cells displayed a four-fold increase in the therapeutic response when treated with radiation as compared to untargeted ones. There was a modest increase in the DNA damage for radiated cells with nuclear targeted GNPs. This research will establish a more successful NP-based platform for combining more than one treatment modality, such as chemotherapy and radiotherapy, and creates a more aggressive approach in eradicating cancer.
纳米颗粒(NPs)在改善治疗方面的应用处于癌症纳米技术的前沿。金纳米颗粒(GNPs)因其在化疗中作为抗癌药物载体以及在放疗中作为剂量增强剂的能力而被广泛使用。研究中使用的GNPs主要定位于细胞质中。然而,如果纳米颗粒能够有效地靶向进入细胞核,治疗反应可以进一步增强。在此,我们提出一种设计用于核靶向的GNP-肽复合物的有效策略。将两种肽缀合到纳米颗粒上:一种肽增强摄取,而另一种肽增强核递送。与未靶向的细胞相比,经辐射处理的核靶向细胞的治疗反应增加了四倍。核靶向GNPs的辐射细胞的DNA损伤有适度增加。这项研究将建立一个更成功的基于纳米颗粒的平台,用于结合多种治疗方式,如化疗和放疗,并在根除癌症方面创造一种更积极的方法。