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文章:

苯基异硫氰酸酯与索拉非尼在纳米颗粒递送系统中的协同作用:增强三阴性乳腺癌治疗效果

Synergistic Action of Benzyl Isothiocyanate and Sorafenib in a Nanoparticle Delivery System for Enhanced Triple-Negative Breast Cancer Treatment

原文发布日期:26 April 2024

DOI: 10.3390/cancers16091695

类型: Article

开放获取: 是

 

英文摘要:

Triple-negative breast cancer (TNBC) presents a therapeutic challenge due to its complex pathology and limited treatment options. Addressing this challenge, our study focuses on the effectiveness of combination therapy, which has recently become a critical strategy in cancer treatment, improving therapeutic outcomes and combating drug resistance and metastasis. We explored a novel combination therapy employing Benzyl isothiocyanate (BITC) and Sorafenib (SOR) and their nanoformulation, aiming to enhance therapeutic outcomes against TNBC. Through a series of in vitro assays, we assessed the cytotoxic effects of BITC and SOR, both free and encapsulated. The BITC–SOR-loaded nanoparticles (NPs) were synthesized using an amphiphilic copolymer, which demonstrated a uniform spherical morphology and favorable size distribution. The encapsulation efficiencies, as well as the sustained release profiles at varied pH levels, were quantified, revealing distinct kinetics that were well-modeled by the Korsmeyer–Peppas equation. The NP delivery system showed a marked dose-dependent cytotoxicity towards TNBC cells, with an IC50 of 7.8 μM for MDA-MB-231 cells, indicating improved efficacy over free drugs, while exhibiting minimal toxicity toward normal breast cells. Furthermore, the NPs significantly inhibited cell migration and invasion in TNBC models, surpassing the effects of free drugs. These findings underscore the potential of BITC–SOR-NPs as a promising therapeutic approach for TNBC, offering targeted delivery while minimizing systemic toxicity.

 

摘要翻译: 

三阴性乳腺癌因其病理复杂且治疗选择有限,构成临床治疗难题。针对这一挑战,本研究聚焦联合疗法的有效性——该策略近年来已成为癌症治疗的关键手段,能够提升疗效并克服耐药与转移问题。我们探索了一种采用异硫氰酸苄酯与索拉非尼及其纳米制剂的新型联合疗法,旨在增强对三阴性乳腺癌的治疗效果。通过系列体外实验,我们评估了游离态与包封态药物的细胞毒性作用。采用两亲性共聚物成功合成负载异硫氰酸苄酯-索拉非尼的纳米颗粒,该颗粒呈现均匀球形形态与良好的粒径分布。定量分析显示,在不同pH条件下的包封效率与缓释曲线呈现符合Korsmeyer-Peppas方程的独特动力学特征。该纳米递送系统对三阴性乳腺癌细胞表现出显著的剂量依赖性细胞毒性,对MDA-MB-231细胞的半数抑制浓度为7.8 μM,疗效优于游离药物,同时对正常乳腺细胞毒性极低。此外,纳米颗粒在三阴性乳腺癌模型中显著抑制细胞迁移与侵袭能力,效果超越游离药物。这些发现凸显了异硫氰酸苄酯-索拉非尼纳米颗粒作为三阴性乳腺癌新型治疗策略的潜力,既能实现靶向递送,又可最大限度降低系统毒性。

 

原文链接:

Synergistic Action of Benzyl Isothiocyanate and Sorafenib in a Nanoparticle Delivery System for Enhanced Triple-Negative Breast Cancer Treatment

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