顺铂是口腔癌治疗中最有效的化疗药物之一，但全身给药有副作用。本研究的目的是评估离子电渗疗法对顺铂封装的壳聚糖纳米颗粒中增强顺铂释放的影响。壳聚糖与三聚磷酸盐（TPP）不同质量比（5:1、10:1、15:1）的效果, 20:1) 对顺铂的包封效率进行了研究。使用共焦激光扫描显微镜观察细胞对顺铂封装的壳聚糖的摄取。使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物测定法检查不同顺铂浓度下的细胞活力。使用三种离子电渗法，即恒流计时电位法（CCCP）、循环计时电位法（CCP）和微分脉冲伏安法（DPV）来增强顺铂封装的壳聚糖纳米颗粒中顺铂的释放。此外，将小鼠口腔鳞状细胞癌细胞系植入小鼠口腔粘膜以诱导口腔癌。评估了 CCCP、CCP 和 DPV 增强顺铂释放对小鼠肿瘤抑制的作用。处死后分离肿瘤和淋巴结进行苏木精-伊红染色和免疫组织化学染色，包括Ki-67和泛CK。采用电感耦合等离子体质谱法定量肿瘤内铂含量。结果显示，质量比为15:1的纳米颗粒表现出最高的顺铂包封率（约15.6%）和最长的持续释放（长达35天）在磷酸盐缓冲盐水中释放率为100%。细胞摄取结果表明壳聚糖纳米颗粒通过内吞作用递送至细胞质。 MTT法结果显示，随着顺铂浓度的增加，细胞的存活率降低。 CCP（1 mA，开：关= 1 s：1 s）和DPV（0-0.06 V）组抑制肿瘤生长最有效，且两组Ki-67阳性和泛CK阳性百分比最低这项研究首次调查并确定了 DPV 在增强纳米颗粒体内药物释放以治疗动物癌症方面的功效。结果表明，CCP 和 DPV 方法有可能与手术相结合治疗口腔癌。© 2024 Chen 等人。

Cisplatin is one of the most effective chemotherapeutic drugs used in oral cancer treatment, but systemic administration has side effects. The purpose of this study was to evaluate the effect of iontophoresis on the enhancement of cisplatin release from cisplatin-encapsulated chitosan nanoparticles.The effect of different mass ratios of chitosan to tripolyphosphate (TPP) (5:1, 10:1, 15:1, 20:1) on the encapsulation efficiency of cisplatin was investigated. Uptake of cisplatin-encapsulated chitosan by cells was observed using a confocal laser scanning microscope. The cell viability at different cisplatin concentrations was examined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Three iontophoresis methods, namely constant-current chronopotentiometry (CCCP), cyclic chronopotentiometry (CCP), and differential pulse voltammetry (DPV), were used to enhance cisplatin release from cisplatin-encapsulated chitosan nanoparticles. In addition, mouse oral squamous cell carcinoma cell lines were implanted into the mouse oral mucosa to induce oral cancer. The effects of enhanced cisplatin release by CCCP, CCP, and DPV on tumor suppression in mice were evaluated. Tumors and lymph nodes were isolated for hematoxylin-eosin staining and immunohistochemistry staining including Ki-67 and pan CK after sacrifice. Inductively coupled plasma mass spectrometry was conducted to quantify the platinum content within the tumors.The results showed that nanoparticles with a mass ratio of 15:1 exhibited the highest cisplatin encapsulation efficiency (approximately 15.6%) and longest continued release (up to 35 days) in phosphate buffered saline with a release rate of 100%. Cellular uptake results suggested that chitosan nanoparticles were delivered to the cytoplasm via endocytosis. The results of the MTT assay revealed that the survival rate of cells decreased as the cisplatin concentration increased. The CCP (1 mA, on:off = 1 s: 1 s) and DPV (0-0.06 V) groups were the most effective in inhibiting tumor growth, and both groups exhibited the lowest percentage of Ki-67 positive and pan CK positive.This study is the first to investigate and determine the efficacy of DPV in enhancing in vivo drug release from nanoparticles for the treatment of cancer in animals. The results suggest that the CCP and DPV methods have the potential to be combined with surgery for oral cancer treatment.© 2024 Chen et al.