在小鼠模型中,以顺铂封装的壳聚糖纳米颗粒的离子粒细胞增强的颊液递送用于治疗口腔癌
Iontophoresis-Enhanced Buccal Delivery of Cisplatin-Encapsulated Chitosan Nanoparticles for Treating Oral Cancer in a Mouse Model
影响因子:6.50000
分区:医学2区 / 药学2区 纳米科技3区
发表日期:2024
作者:
Yi-Wen Chen, Ai-Chia He, Tzu-Yun Huang, De-Hao Lai, Yi-Ping Wang, Wei-Wen Liu, Wei-Ting Kuo, Hsin-Han Hou, Shih-Jung Cheng, Chen-Yi Lee, Wei-Chun Chuang, Che-Chen Chang, Bor-Shiunn Lee
摘要
顺铂是在口腔癌治疗中使用的最有效的化学治疗药物之一,但全身给药具有副作用。这项研究的目的是评估离子噬菌体对从顺铂封闭的壳聚糖构壳纳米颗粒增强顺铂释放的影响。壳聚糖与三聚磷酸酯(TPP)不同质量比的影响(5:1,10:1,10:1,15:1,20:1,20:1)对CONAPPUTION cONSPASPUTION cONSPASTATINATS cONSISPLATIT ASSISPLATIN aSISISATIN的影响。使用共共聚焦激光扫描显微镜观察到了顺铂封装的壳聚糖。使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基二甲基二唑烷溴化物测定法检查了不同顺铂浓度下的细胞活力。使用三种离子噬菌体方法,即恒定计时元素计量法(CCCP),环状计时元素计(CCP)和差分脉冲伏安电电疗法(DPV),用于增强从顺铂释放的顺铂释放,从顺铂释放。另外,将小鼠口服鳞状细胞癌细胞系植入小鼠口服粘膜中以诱导口腔癌。评估了CCCP,CCP和DPV对小鼠肿瘤抑制的增强顺铂释放的影响。分离肿瘤和淋巴结,以进行苏木精 - 欧生染色和免疫组织化学染色,包括Ki-67和PAN CK,牺牲后。进行了电感耦合等离子体质谱法以量化肿瘤内的铂含量。结果表明,质量比为15:1的纳米颗粒表现出顺铂的封装效率最高(约15.6%),持续释放(约15.6%),并在磷酸盐的释放中释放最长(最多35天),含有100%的释放速率。细胞摄取结果表明,壳聚糖纳米颗粒通过内吞作用传递到细胞质。 MTT分析的结果表明,随着顺铂浓度的增加,细胞的存活率降低。 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.结果表明,CCP和DPV方法具有与口腔癌治疗的手术相结合的潜力。
Abstract
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.