Enhancement of Anticancer Efficacy and Tumor Penetration of Sorafenib by Ionic Liquids,Advanced Healthcare Materials

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Enhancement of Anticancer Efficacy and Tumor Penetration of Sorafenib by Ionic Liquids
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2020-11-17 , DOI: 10.1002/adhm.202001455
Yujie Shi _{1,

2} , Zongmin Zhao _{1,

3} , Kevin Peng _{1,

3} , Yongsheng Gao _{1,

3} , Debra Wu _{1,

3} , Jayoung Kim _{1,

3} , Samir Mitragotri _{1,

3}

Affiliation

Ionic liquids (ILs) possess unique solvation and biological properties for drug delivery. Choline and geranic acid (CAGE) in particular, has been successfully formulated to orally deliver insulin and hydrophobic therapeutics such as sorafenib (SRF). However, relatively little is known about the effect of CAGE on intracellular delivery of drugs. Here the effect of low‐concentration CAGE (<2 mg mL⁻¹) on the delivery of SRF into cancer cells (4T1, PANC‐1, and HT29) as well as intestine epithelium cells (Caco‐2) is studied. The anti‐cancer effect of SRF is enhanced by up to fivefold in the presence of CAGE (0.5 mg mL⁻¹). The effect is mediated not by enhancing the cellular uptake of SRF but by improving intracellular SRF retention by inhibiting exocytosis. Moreover, CAGE improves the anti‐tumor effect of SRF by increasing apoptosis and blocking cell‐cycle progression. Moreover, CAGE significantly enhances the penetration of SRF into and across multicellular constructs with multiple mechanisms involved. Collectively, the administration of ILs such as CAGE combined with SRF may offer a novel therapy to better inhibit tumor progression.

中文翻译：

离子液体增强索拉非尼的抗癌功效和肿瘤穿透力

离子液体（ILs）具有独特的溶剂化和生物特性，可用于药物输送。特别是胆碱和香叶酸（CAGE）已成功配制成口服胰岛素和疏水性治疗药物，例如索拉非尼（SRF）。然而，关于CAGE对药物细胞内递送的作用的了解相对较少。在此研究了低浓度CAGE（<2 mg mL ^-1）对SRF递送至癌细胞（4T1，PANC-1和HT29）以及肠上皮细胞（Caco-2）的影响。存在CAGE（0.5 mg mL ^-1时），SRF的抗癌作用增强了五倍）。该作用不是通过增强细胞对SRF的吸收来介导的，而是通过抑制胞吐作用来改善细胞内SRF的保留来介导的。此外，CAGE通过增加细胞凋亡和阻断细胞周期进程来改善SRF的抗肿瘤作用。此外，CAGE可通过多种机制显着增强SRF进入多细胞构建体的穿透能力。总体上讲，ILs（如CAGE）与SRF联合给药可能会提供一种新的疗法，以更好地抑制肿瘤的进展。

更新日期：2021-01-20

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