Serotonin-Functionalized Vit-E Nanomicelles for Targeting of Irinotecan to Prostate Cancer Cells,ACS Applied Bio Materials

当前位置： X-MOL 学术 › ACS Appl. Bio Mater. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Serotonin-Functionalized Vit-E Nanomicelles for Targeting of Irinotecan to Prostate Cancer Cells
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2020-07-01 , DOI: 10.1021/acsabm.0c00579
Lakshmi Tunki _{1,

2} , Ashok Kumar Jangid ₃ , Deep Pooja ₂ , Suresh Kumar Bhargava ₂ , Ramakrishna Sistla ₁ , Hitesh Kulhari ₃

Affiliation

Receptor-mediated endocytosis is key in the success of targeted nanomedicines for the treatment of cancer. Various receptors have been explored for the active targeting of anticancer drugs to avoid the drawbacks of conventional anticancer drugs. This research work aimed to investigate the potential of serotonin (ST)-conjugated Vit-E nanomicelles for the targeted delivery of irinotecan hydrochloride (IRI) to human prostate cancer cells. A ST receptor-targeting conjugate was synthesized by conjugating ST and d-α-tocopheryl polyethylene glycol succinate via a two-step synthesis reaction. The developed formulation demonstrated a size of about 14 nm, a negative zeta potential of around −20 mV, a high drug encapsulation efficiency, and sustained drug release over 48 h. Cytotoxicity studies revealed that ST-conjugated, IRI-loaded nanomicelles (IRI-STNM) were not only toxic to human prostate cancer cells but also eradicate these cells present in the form of 3D spheroids. This cytotoxicity of IRI-STNM was mediated through induction of apoptosis, reactive oxygen species generation, change in mitochondrial membrane potential, and inhibition of cell migration. Further, IRI-STNM performed significantly better than the native IRI and nontargeted nanomicelles, which was led by a higher cellular uptake of IRI-STNM, indicating the role of ST in targeting of drug-loaded nanomicelles.

中文翻译：

5-羟色胺功能化 Vit-E 纳米胶束用于靶向伊立替康靶向前列腺癌细胞

受体介导的内吞作用是靶向纳米药物成功治疗癌症的关键。已经探索了各种受体用于抗癌药物的主动靶向，以避免常规抗癌药物的缺点。这项研究工作旨在研究 5-羟色胺 (ST) 缀合的 Vit-E 纳米胶束将盐酸伊立替康 (IRI) 靶向递送至人前列腺癌细胞的潜力。通过缀合 ST 和d合成 ST 受体靶向缀合物-α-生育酚聚乙二醇琥珀酸酯通过两步合成反应。开发的制剂显示出约 14 nm 的尺寸、约 -20 mV 的负 zeta 电位、高药物包封效率和超过 48 小时的持续药物释放。细胞毒性研究表明，ST 偶联、载有 IRI 的纳米胶束 (IRI-STNM) 不仅对人类前列腺癌细胞有毒，而且还能根除以 3D 球体形式存在的这些细胞。IRI-STNM 的这种细胞毒性是通过诱导细胞凋亡、活性氧生成、线粒体膜电位变化和抑制细胞迁移来介导的。此外，IRI-STNM 的性能明显优于天然 IRI 和非靶向纳米胶束，这是由 IRI-STNM 的更高细胞摄取率导致的，

更新日期：2020-08-17

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11