Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, People's Republic of China.
Department of Pediatric and Preventive Dentistry, Shanxi Medical University School and Hospital of Stomatology, Taiyuan, Shanxi, People's Republic of China.
Int J Nanomedicine. 2023 Jun 17;18:3309-3324. doi: 10.2147/IJN.S402249. eCollection 2023.
Oral squamous cell carcinoma (OSCC) is a malignant disease with serious impacts on human health and quality of life worldwide. This disease is traditionally treated through a combination of surgery, radiotherapy, and chemotherapy. However, the efficacy of traditional treatments is hindered by systemic toxicity, limited therapeutic effects, and drug resistance. Fibroblast activation protein (FAP) is a membrane-bound protease. Although FAP has limited expression in normal adult tissues, it is highly expressed in the tumor microenvironment of many solid cancers - a characteristic that makes it an ideal target for anticancer therapy. In this study, we constructed a nano-drug delivery system (NPF@DOX) targeting FAP to increase the therapeutic efficiency of synergistic chemo-photothermal therapy against OSCC.
We utilized PEGylated nano-graphene oxide (NGO) to link doxorubicin (DOX) and fluorescently-labeled, FAP-targeted peptide chains via hydrogen bonding and π-π bonding to enhance the targeting capability of NPF@DOX. The synthesis of NPF@DOX was analyzed using UV-Vis and FT-IR spectroscopy and its morphology using transmission electron microscopy (TEM). Additionally, the drug uptake efficiency in vitro, photo-thermal properties, release performance, and anti-tumor effects of NPF@DOX were evaluated and further demonstrated in vivo.
Data derived from FT-IR, UV-Vis, and TEM implied successful construction of the NPF@DOX nano-drug delivery system. Confocal laser scanning microscopy images and in vivo experiments demonstrated the targeting effects of FAP on OSCC. Furthermore, NPF@DOX exhibited a high photothermal conversion efficiency (52.48%) under near-infrared radiation. The thermogenic effect of NPF@DOX simultaneously promoted local release of DOX and apoptosis based on a pH-stimulated effect. Importantly, FAP-targeted NPF@DOX in combination with PTT showed better tumor suppression performance in vivo and in vitro than did either therapy individually.
NPF@DOX can precisely target OSCC, and combined treatment with chemical and photothermal therapy can improve the therapeutic outcomes of OSCC. This method serves as an efficient therapeutic strategy for the development of synergistic anti-tumor research.
口腔鳞状细胞癌（OSCC）是一种严重危害全球人类健康和生活质量的恶性疾病。传统上，这种疾病通过手术、放疗和化疗相结合来治疗。然而，传统治疗的疗效受到全身毒性、治疗效果有限和耐药性的限制。成纤维细胞激活蛋白（FAP）是一种膜结合蛋白酶。尽管 FAP 在正常成人组织中的表达有限，但在许多实体癌的肿瘤微环境中高度表达——这一特征使其成为抗癌治疗的理想靶点。在这项研究中，我们构建了一种针对 FAP 的纳米药物递送系统（NPF@DOX），以提高协同化疗-光热治疗 OSCC 的治疗效率。
我们利用聚乙二醇化纳米氧化石墨烯（NGO）通过氢键和π-π 键将阿霉素（DOX）和荧光标记的、靶向 FAP 的肽链连接起来，以增强 NPF@DOX 的靶向能力。通过紫外可见分光光度计和傅里叶变换红外光谱分析了 NPF@DOX 的合成，并通过透射电子显微镜（TEM）分析了其形态。此外，还评估了 NPF@DOX 的体外摄取效率、光热性能、释放性能和抗肿瘤效果，并在体内进一步进行了验证。
FT-IR、UV-Vis 和 TEM 数据表明成功构建了 NPF@DOX 纳米药物递送系统。共聚焦激光扫描显微镜图像和体内实验证明了 FAP 对 OSCC 的靶向作用。此外，NPF@DOX 在近红外辐射下表现出高的光热转换效率（52.48%）。NPF@DOX 的热致效应同时促进了 DOX 的局部释放和基于 pH 刺激效应的细胞凋亡。重要的是，与单独的 PTT 相比，FAP 靶向的 NPF@DOX 联合 PTT 在体内和体外均表现出更好的肿瘤抑制效果。
NPF@DOX 可以精确靶向 OSCC，化学和光热联合治疗可以提高 OSCC 的治疗效果。该方法为协同抗肿瘤研究的发展提供了一种有效的治疗策略。
