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The Synergistic Anticancer Effect of Dual Drug- (Cisplatin/Epigallocatechin Gallate) Loaded Gelatin Nanoparticles for Lung Cancer Treatment
Journal of Nanomaterials ( IF 3.791 ) Pub Date : 2020-08-05 , DOI: 10.1155/2020/9181549
Yin-Ju Chen, Zhi-Weng Wang, Tung-Ling Lu, Clinton B. Gomez, Hsu-Wei Fang, Yang Wei, Ching-Li Tseng

Lung cancer has the highest mortality of any cancer worldwide, and cisplatin is a first-line chemotherapeutic agent for lung cancer treatment. Unfortunately, cisplatin resistance is a common cause of therapeutic failure. The ability to overcome chemoresistance is crucial to the effective treatment of lung cancer. Recently, epigallocatechin gallate (EGCG), a type of polyphenol extracted from tea, has been shown to suppress the rapid proliferation of cancer cells, including lung cancer. We tested whether nanoparticles (NPs) carrying a dual drug load, cisplatin and EGCG, could overcome chemoresistance to cisplatin, by working together to kill lung cancer cells. Self-assembling gelatin/EGCG nanoparticles (GE) were synthesized, and cisplatin was then incorporated, to construct a dual drug nanomedicine (EGCG/cisplatin-loaded gelatin nanoparticle, named as GE-Pt NP). The particle size and zeta potential were examined by dynamic light scattering (DLS). The morphological structure of GE-Pt NPs was observed by transmission electron microscopy (TEM). In vitro testing was performed using a human lung adenocarcinoma cell line (A549). A cytotoxicity examination was performed, using a WST-8 cell proliferation assay. Intracellular cisplatin content was quantified by inductively coupled plasma mass spectrometry (ICP-MS). In conclusion, we successfully prepared GE-Pt NPs, as spherical structures, approximately 75 nm in diameter, with a positive charge (). The encapsulation rate of cisplatin in GE-Pt was about 63.7%, and the EGCG loading rate was around 89%. A relatively low concentration of GE-Pt NPs (EGCG 5 μg/mL : cisplatin 2 μg/mL) exhibited significant cytotoxicity, compared to cisplatin alone. The GE-Pt NPs are freely taken up by cells via endocytosis, raising the intracellular cisplatin concentration to a therapeutic level. We consider that combination therapy of cisplatin and EGCG in nanoparticles (GE-Pt NPs) may help overcome cisplatin resistance and could effectively be used in the treatment of lung cancer.

中文翻译:

载有明胶(顺铂/表没食子儿茶素没食子酸酯)的明胶纳米颗粒对肺癌的协同抗癌作用

肺癌是全球所有癌症中死亡率最高的,顺铂是用于肺癌治疗的一线化疗药物。不幸的是,顺铂耐药性是治疗失败的常见原因。克服化学抗性的能力对于有效治疗肺癌至关重要。最近,表没食子儿茶素没食子酸酯(EGCG)是一种从茶中提取的多酚,已被证明可抑制包括肺癌在内的癌细胞的快速增殖。我们测试了携载双重药物顺铂和EGCG的纳米颗粒(NPs)是否可以通过共同杀死肺癌细胞来克服对顺铂的化学耐药性。合成了自组装明胶/ EGCG纳米颗粒(GE),然后掺入了顺铂,以构建双重药物纳米药物(负载EGCG /顺铂的明胶纳米颗粒,命名为GE-Pt NP)。通过动态光散射(DLS)检查了粒度和ζ电势。通过透射电子显微镜(TEM)观察到GE-Pt NP的形态结构。使用人肺腺癌细胞系(A549)进行了体外测试。使用WST-8细胞增殖测定法进行了细胞毒性检查。细胞内顺铂含量通过电感耦合等离子体质谱法(ICP-MS)进行定量。总之,我们成功地制备了球形的GE-Pt NP,直径约为75 nm,带有正电荷()。顺铂在GE-Pt中的包封率约为63.7%,EGCG负载率约为89%。GE-铂NP的相对低浓度(EGCG 5  μ克/毫升:顺铂2  μ克/毫升)表现出的细胞毒性显著相比,单独的顺铂。GE-Pt NP被细胞通过内吞作用自由吸收,从而将细胞内顺铂浓度提高到治疗水平。我们认为在纳米颗粒(GE-Pt NPs)中顺铂和EGCG的联合治疗可能有助于克服顺铂耐药性,可以有效地用于治疗肺癌。
更新日期:2020-08-06
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