Thermosensitive hydrogels for sustained-release of sorafenib and selenium nanoparticles for localized synergistic chemoradiotherapy.,Biomaterials

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Thermosensitive hydrogels for sustained-release of sorafenib and selenium nanoparticles for localized synergistic chemoradiotherapy.
Biomaterials ( IF 12.8 ) Pub Date : 2019-05-22 , DOI: 10.1016/j.biomaterials.2019.05.031
Lan Zheng ₁ , Chang'e Li ₁ , Xiaoting Huang ₁ , Xueran Lin ₁ , Weiqiang Lin ₁ , Fang Yang ₁ , Tianfeng Chen ₁

Affiliation

In this study, we synthesized a thermosensitive composite of Gel-SOR-LUF-SeNPs to achieve the localized synergistic chemoradiotherapy of hepatocellular carcinoma (HCC). Sorafenib (SOR) is one of the important clinical drugs for unresectable and advanced HCC. However, the uncontrollable release of SOR induced drug resistance and severe side effects. Recently, thermosensitive hydrogels have emerged as promising drug-delivery carriers, due to their superior advantages including biodegradability, low-toxicity, high drug loading, site-specificity, sustained and controlled drug release behavior. We synthesized the thermosensitive hydrogel nanosystem (Gel-SOR-LUF-SeNPs) as an effective drug release depot with the combination of radiotherapy for the localized and sustained treatment of HCC. The results showed that SOR was released continuously from Gel-SOR-LUF-SeNPs with the degradation of the hydrogel for a prolonged period (over 15 days). The combination of localized and chemoradiotherapy accelerated the apoptosis of HepG2 cells through reducing the expression of Ki67 and CD34, and activating caspase-3 signaling pathway. Further studies demonstrated that this nanosystem showed site-specific and long-term anticancer effects in mice up to 21 days after single subcutaneous injection, and no obvious side effects of mice were found. Taken together, this study presents a local and long-term treatment for HCC, which may shed light on unresectable HCC therapy in the future.

中文翻译：

用于索拉非尼和硒纳米粒子缓释的热敏水凝胶，用于局部协同放化疗。

在这项研究中，我们合成了Gel-SOR-LUF-SeNPs的热敏复合材料，以实现肝细胞癌（HCC）的局部协同放化疗。索拉非尼（SOR）是不可切除和晚期HCC的重要临床药物之一。然而，无法控制的SOR释放引起耐药性和严重的副作用。近来，热敏水凝胶由于其优越的优势包括生物可降解性，低毒性，高载药量，位点特异性，持续和受控的药物释放行为，已经成为有希望的药物传递载体。我们合成了热敏水凝胶纳米系统（Gel-SOR-LUF-SeNPs）作为有效的药物释放库，结合放疗对肝癌的局部和持续治疗。结果表明，SOR从Gel-SOR-LUF-SeNPs中连续释放，且水凝胶降解时间延长（超过15天）。局部放化疗联合通过降低Ki67和CD34的表达以及激活caspase-3信号通路来加速HepG2细胞的凋亡。进一步的研究表明，这种纳米系统在单次皮下注射后长达21天对小鼠显示出特定部位的长期抗癌作用，并且未发现明显的小鼠副作用。综上所述，本研究提出了一种针对HCC的局部和长期治疗方法，这可能为将来不可切除的HCC治疗提供启示。局部放化疗联合通过降低Ki67和CD34的表达以及激活caspase-3信号通路来加速HepG2细胞的凋亡。进一步的研究表明，这种纳米系统在单次皮下注射后长达21天对小鼠显示出特定部位的长期抗癌作用，并且未发现明显的小鼠副作用。综上所述，本研究提出了一种针对HCC的局部和长期治疗方法，这可能为将来不可切除的HCC治疗提供启示。局部放化疗联合通过降低Ki67和CD34的表达以及激活caspase-3信号通路来加速HepG2细胞的凋亡。进一步的研究表明，这种纳米系统在单次皮下注射后长达21天对小鼠显示出特定部位的长期抗癌作用，并且未发现明显的小鼠副作用。综上所述，本研究提出了一种针对HCC的局部和长期治疗方法，这可能为将来不可切除的HCC治疗提供启示。

更新日期：2019-05-23

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