Combined Chemo-Photothermal Therapy of Oral Carcinoma Based on Doxorubicin-Loaded Gold Flower Nanocomposites

摘要

Multifunctional nanomaterials have been widely investigated for cancer therapy. In our previous studies, we have successfully fabricated a nanocarrier composed of gold nanoflowers (AuNFs), which are coated with two layers of silica for doxorubicin (DOX) loading (Au@Si@mSi-DOX). Moreover, the experiments of cancer treatment as well as the mechanism of cancer inhibition have been tested both in vitro and in vivo. Herein, the synergistic anti-tumor effect of combined chemo-photothermal therapy was conducted by oral cancer cell line Cal-27 cells and the nude mice model. As expected, compared with photothermal therapy (PTT) or chemotherapy alone, the combined chemo-photothermal therapy conducted by Au@Si@mSi-DOX post-irradiation showed enhanced anti-tumor effect. Au@Si@mSi-DOX exhibited minor cytotoxicity before irradiation but its proliferation is intensively dropped upon post-irradiation by NIR laser (808 nm, 2.7 W/cm(2)). The intratumoral injection of Au@Si@mSi-DOX under NIR laser radiation (808 nm, 3.75 W/cm(2)) has induced more significant tumor inhibition. The inhibition efficacy was 25.53% (Au@Si@mSi), 126.92% (DOX), 51.28% (Au@Si@mSi-DOX), 22.92% (PBS + laser), 210.53% (Au@Si@mSi + laser), 96.67% (DOX + laser), 742.86% (Au@Si@mSi-DOX + laser), respectively compared to PBS group. Apoptosis is considered to be the mechanism during the process of anti-tumor effect. More apoptosis could be induced in the group cells of Au@Si@mSi-DOX plus laser irradiation than the cells of free DOX or Au@Si@mSi plus laser irradiation. The corresponding difference of typical apoptotic protein, BAX/BCL-2, CASPASE 3 had taken place. Meanwhile, histological analysis confirmed the good biocompatibility of this nanomaterial. These results suggested the synergetic anti-cancer effect of chemo-photothermal therapy could be mediated by this multifunctional nanomaterial. The results also highlighted the remarkable potential of Au@Si@mSi-DOX in photothermal controllable tumor treatment. The nanomaterial is believed to have broad potential applications in malignant tumour therapy including oral cancers.