Hyaluronic Acid Modified Au@SiO2@Au Nanoparticles for Photothermal Therapy of Genitourinary Tumors

Abstract

Bladder cancer and prostate cancer are the most common malignant tumors of the genitourinary system. Conventional strategies still face great challenges of high recurrence rate and severe trauma. Therefore, minimally invasive photothermal therapy (PTT) has been extensively explored to address these challenges. Herein, fluorescent Au nanoparticles (NPs) were first prepared using glutathione as template, which were then capped with SiO2 shell to improve the biocompatibility. Next, Au nanoclusters were deposited on the NPs surface to obtain Au@SiO2@Au NPs for photothermal conversion. The gaps between Au nanoparticles on their surface could enhance their photothermal conversion efficiency. Finally, hyaluronic acid (HA), which targets cancer cells overexpressing CD44 receptors, was attached on the NPs surface via 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) chemistry to improve the accumulation of NPs in tumor tissues. Photothermal experiments showed that NPs with an average size of 37.5 nm have a high photothermal conversion efficiency (47.6%) and excellent photostability, thus exhibiting potential application as a PTT agent. The temperature of the NPs (100 μg·mL−1) could rapidly increase to 38.5 °C within 200 s and reach the peak of 57.6 °C with the laser power density of 1.5 W·cm−2 and irradiation time of 600 s. In vivo and in vitro PTT experiments showed that the NPs have high biocompatibility and excellent targeted photothermal ablation capability of cancer cells. Both bladder and prostate tumors disappeared at 15 and 18 d post-treatment with HA-Au@SiO2@Au NPs, respectively, and did not recur. In summary, HA-Au@SiO2@Au NPs can be used a powerful PTT agent for minimally invasive treatment of genitourinary tumors.