Department of Preventive Dentistry, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, People's Republic of China.
Department of Sports and Health, Guangzhou Sport University, Guangzhou, People's Republic of China.
Int J Nanomedicine. 2024 Mar 13;19:2611-2623. doi: 10.2147/IJN.S452060. eCollection 2024.
The photodynamic therapy (PDT) showed promising potential in treating tongue squamous cell carcinoma (TSCC). The Food and Drug Administration approved Verteporfin (Ver) is a powerful alternative in this field for its penetrating power and high production of reactive oxygen species (ROS). However, its applications in the treatment of TSCC are still rare.
Ver was loaded onto Poly (lactic-co-glycolic acid) (PLGA) nanoparticles, followed by the modification with RGD peptide as the ligand. The nanostructured was named as RPV. In vitro assessments were conducted to evaluate the cytotoxicity of RPV through the Live/Dead assay analysis and Cell Counting Kit-8 (CCK-8) assay. Using the reactive oxygen species assay kit, the potential for inducing targeted tumor cell death upon laser irradiation by promoting ROS production was investigated. In vivo experiments involved with the biological distribution of RPV, the administration with RPV followed by laser irradiation, and the measurement of the tumor volumes. Immunohistochemical analysis was used to detect the Ki-67 expression, and apoptosis induced by RPV-treated group. Systemic toxicity was evaluated through hematoxylin-eosin staining and blood routine analysis. Real-time monitoring was employed to track RPV accumulation at tumor sites.
The in vitro assessments demonstrated the low cytotoxicity of RPV and indicated its potential for targeted killing TSCC cells under laser irradiation. In vivo experiments revealed significant tumor growth inhibition with RPV treatment and laser irradiation. Immunohistochemical analysis showed a notable decrease in Ki-67 expression, suggesting the effective suppression of cell proliferation, and TUNEL assay indicated the increased apoptosis in the RPV-treated group. Pathological examination and blood routine analysis revealed no significant systemic toxicity. Real-time monitoring exhibited selective accumulation of RPV at tumor sites.
The findings collectively suggest that RPV holds promise as a safe and effective therapeutic strategy for TSCC, offering a combination of targeted drug delivery with photodynamic therapy.
光动力疗法（PDT）在治疗舌鳞状细胞癌（TSCC）方面显示出巨大的潜力。美国食品和药物管理局批准的维替泊芬（Ver）因其穿透力强和产生大量活性氧（ROS）而成为该领域的有力选择。然而，其在 TSCC 治疗中的应用仍较为罕见。
将 Ver 负载到聚（乳酸-共-乙醇酸）（PLGA）纳米颗粒上，然后用 RGD 肽作为配体进行修饰。该纳米结构被命名为 RPV。通过 Live/Dead 分析和细胞计数试剂盒-8（CCK-8）分析评估 RPV 的体外细胞毒性。使用活性氧检测试剂盒，研究通过促进 ROS 产生激光照射诱导靶向肿瘤细胞死亡的能力。体内实验涉及 RPV 的生物分布、给予 RPV 后激光照射以及肿瘤体积测量。免疫组织化学分析用于检测 Ki-67 表达和 RPV 处理组诱导的细胞凋亡。通过苏木精-伊红染色和血常规分析评估系统毒性。采用实时监测跟踪 RPV 在肿瘤部位的积累。
体外评估表明 RPV 的细胞毒性较低，并表明其在激光照射下具有靶向杀伤 TSCC 细胞的潜力。体内实验表明，给予 RPV 和激光照射可显著抑制肿瘤生长。免疫组织化学分析显示 Ki-67 表达明显减少，提示细胞增殖得到有效抑制，TUNEL 检测表明 RPV 处理组细胞凋亡增加。病理检查和血常规分析显示无明显系统毒性。实时监测显示 RPV 在肿瘤部位有选择性聚集。
研究结果表明，RPV 作为治疗 TSCC 的一种安全有效的治疗策略具有潜力，它提供了靶向药物递送与光动力疗法的结合。
