In this work, we have successfully designed and formulated a hybrid polypeptide-based multilayer assembled gold nanorod (DH-GNR). We have hypothesized that near infrared (NIR) laser irradiation of DH-GNR will combine the benefits of chemotherapy and photothermal therapy. The GNR was surface functionalized with poly-glutamic acid (PGA) and poly-L-Lysine (PLL) with a final layer of hyaluronic acid (HA) that could also serve as a targeting ligand towards the overexpressed CD44 receptors in ovarian cancer cells. The zigzag zeta potential of nanoparticle is a proof of successfully assembly of alternative polymers on the GNR surface. NIR irradiation exhibited a burst release of drug in pH 7.4 and pH 5.0 buffer conditions. The combination of doxorubicin (DOX)-based chemotherapy and GNR-based photothermal therapy exhibited a synergistic effect in killing the SKOV3 cancer cells. DH-GNR(+NIR) induced a 82.5% apoptosis (combined early and late apoptosis) compared to only 35.2% and 38.5% for DOX or DH-GNR(-NIR) treated cell group. Results clearly suggest that the excessive ROS generation in DH-GNR (+NIR) might be responsible for the cell apoptosis and cell death. The promising anticancer effect of DH-GNR will be of great potential in the treatment of ovarian cancers and worth the further development for treating other malignant tumors.

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