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.
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