A cellular/intranuclear dual-targeting nanoplatform based on gold nanostar for accurate tumor photothermal therapy

In this work, a cellular/intranuclear dual-targeting nanoplatform was designed for tumor photothermal therapy (PTT). As a photo-to-heat nanoheater, a gold nanostar (GNS) was decorated with a nuclear localization sequence (NLS) to form GNS-NLS which possessed nuclear-targeting ability. After that, hyaluronic acid (HA) was coated on the surface of GNS-NLS (GNS-NLS@HA) via electrostatic interaction for tumor cellular recognition and targeting. It was found that by harnessing the recognition of CD44 receptor by HA, GNS-NLS@HA had the ability to target tumor cells accurately, and further be efficaciously internalized into cells with stellate shape. Subsequently, tumor intracellular hyaluronidase (HAase) from the endosome led to the degradation of HA to expose nuclear-targeting nanoheater GNS-NLS, and GNS-NLS was able to enhance PTT efficiency through subcellular nuclear location by a dual-stage near infrared light irradiation strategy. The first stage of light irradiation was of short duration to enhance the subcellular location of the nanoplatform to nuclei, and the second stage of light irradiation was of long duration to achieve admirable photothermal transduction as well as destruction of nuclei. This cellular/intranuclear dual-targeting nanoplatform, GNS-NLS@HA, displayed prominent tumor suppression efficiency both in vitro and in vivo, and inhibited tumor metastasis effectively.