Nuclear-targeted therapy has received increasing attention as a potential strategy to improve the therapeutic efficacy of treating cancer. The main challenges include targeting, drug-delivery efficiency and release of anticancer agents to the cancer cell nucleus. Nanoparticles as nanocarriers have started to address some of these issues. However, a lack of understanding in how nanoconstructs interact with the nucleus has precluded detailed studies. In this article, we highlight a nanoconstruct composed of gold (Au) nanostars loaded with nucleolin-specific aptamers. This nanoconstruct induced major changes in the nuclear phenotype through nuclear envelope (NE) invaginations. Femtosecond, light-triggered release of the aptamers from the surface of the Au nanostars further increased the number of NE deformations. Cancer cells with more NE folding showed increased apoptosis as well as decreased cell viability. The author's of this article have revealed that correlation between drug-induced changes in nuclear phenotypes and increased therapeutic efficacy can provide new insight into nuclear-targeted cancer therapy.
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