Nag Sayoni, Das Saha Krishna
Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, West Bengal, India.
ACS Omega. 2021 Oct 21;6(43):28752-28769. doi: 10.1021/acsomega.1c03477. eCollection 2021 Nov 2.
Colon cancer is the second highest contributor of cancer-related deaths throughout the world. Treatment strategies with tannic acid and vitamin E are envisaged as desirable and safe owing to their robust antioxidative and anti-inflammatory potential. In the present report, these bioactives have been nanoencapsulated in poly(d,l-lactide--glycolic acid) (PLGA) formulations for maintaining sustained release and ensuring enhanced bioavailability. Capping of nanoparticles (NPs) with chitosan was done for enhanced anticancer efficacy and tumor targeting. CS-PLGA-TA-E, administered intraperitoneally, significantly inhibited tumor number and tumor volume and normalized colon histology in the colon cancer. Tissue distribution studies showed that TA/E content from CS-PLGA-TA-E was present in a higher concentration in the tumor tissue than the concentration of TA/E content from PLGA-TA-E or free TA or free E. Also, the TA/E content from all of the treatment groups showed its highest concentration in the tumor compared to other organs. Antioxidant enzymes and proinflammatory cytokines (TNF-α, IL-1β, IL-6) were inhibited by CS-PLGA-TA-E. CS-PLGA-TA-E inhibited markers for tumor growth (EGFR-PI3K-AKT), inflammation (NF-κB/Stat3), β-catenin signaling (β-catenin, c-myc, cyclin D1), EMT (E-cadherin, N-cadherin, vimentin), and apoptosis (Bcl-2) in a significantly greater way as compared with PLGA-TA-E, TA, or E. CS-PLGA-TA-E NPs can be considered promising anticancer drugs for colon cancer.
结肠癌是全球癌症相关死亡的第二大主要原因。由于单宁酸和维生素E具有强大的抗氧化和抗炎潜力，因此将它们作为治疗策略被认为是理想且安全的。在本报告中，这些生物活性物质已被纳米包裹在聚（d，l-丙交酯-乙交酯）（PLGA）制剂中，以维持持续释放并确保提高生物利用度。用壳聚糖对纳米颗粒（NPs）进行封端，以增强抗癌功效和肿瘤靶向性。腹腔注射CS-PLGA-TA-E可显著抑制结肠癌的肿瘤数量和肿瘤体积，并使结肠组织学恢复正常。组织分布研究表明，CS-PLGA-TA-E中的TA/E含量在肿瘤组织中的浓度高于PLGA-TA-E、游离TA或游离E中的TA/E含量浓度。此外，与其他器官相比，所有治疗组的TA/E含量在肿瘤中的浓度最高。CS-PLGA-TA-E可抑制抗氧化酶和促炎细胞因子（TNF-α、IL-1β、IL-6）。与PLGA-TA-E、TA或E相比，CS-PLGA-TA-E能更显著地抑制肿瘤生长标志物（EGFR-PI3K-AKT）、炎症标志物（NF-κB/Stat3）、β-连环蛋白信号通路标志物（β-连环蛋白、c-myc、细胞周期蛋白D1）、上皮-间质转化标志物（E-钙黏蛋白、N-钙黏蛋白、波形蛋白）和凋亡标志物（Bcl-2）。CS-PLGA-TA-E NPs可被认为是有前景的结肠癌抗癌药物。
