Targeted Nano-Drug Delivery of Colchicine against Colon Cancer Cells by Means of Mesoporous Silica Nanoparticles
Targeted Nano-Drug Delivery of Colchicine against Colon Cancer Cells by Means of Mesoporous Silica Nanoparticles
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DOI：
10.3390/cancers12010144
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发表时间：
2020-01-01
期刊：
影响因子：
5.2
通讯作者：
Lojkowski, Witold
中科院分区：
文献类型：
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作者：
AbouAitah, Khaled;Hassan, Heba A.;Lojkowski, Witold
抗癌药物是重要的抗癌药物，包括天然生物碱前体药物秋水仙碱(Col)。然而，使用Col作为抗癌药物的一个主要挑战是它的细胞毒性。我们利用介孔二氧化硅纳米颗粒(MSN)开发了一种新型的COL药物释放系统(DDS)。用膦酸基对MSN进行官能化，负载COL，并用叶酸壳聚糖-甘氨酸复合体包覆MSN。由此产生的名为MSNsPCOL/CG-FA的纳米配方被测试了对癌症和正常细胞系的作用。与COL相比，MSNsPCOL/CG-FA的抗癌作用显著增强。在HCT116细胞中，达到了100%的抑制。MSNsPCOL/CG-FA的有效率依次为：HCT116(结肠癌)和GT；HepG2(肝癌)和GT；PC3(前列腺癌)。在BJ1正常细胞中，MSNsPCOL/CG-FA的细胞毒性(4%)低于COL(接近60%)。对HCT116细胞的作用机制进行了详细的研究，发现主要是由增强的抗分裂效应引起的内源性凋亡。此外，还发现了基因调控(转移相关肺腺癌转录本1(Malat 1)和microRNA(mir-205))和免疫治疗效应(血管生成素-2(Ang-2蛋白)和程序性细胞死亡蛋白1(PD-1))的作用。因此，本研究表明，与游离Col相比，靶向递送的Col具有增强的抗癌作用和降低的细胞毒性，是利用低成本的小分子天然前药开发癌症免疫治疗的一种新方法。
Antimitotics are important anticancer agents and include the natural alkaloid prodrug colchicine (COL). However, a major challenge of using COL as an anticancer drug is its cytotoxicity. We developed a novel drug delivery system (DDS) for COL using mesoporous silica nanoparticles (MSNs). The MSNs were functionalized with phosphonate groups, loaded with COL, and coated with folic acid chitosan-glycine complex. The resulting nanoformulation, called MSNsPCOL/CG-FA, was tested for action against cancer and normal cell lines. The anticancer effect was highly enhanced for MSNsPCOL/CG-FA compared to COL. In the case of HCT116 cells, 100% inhibition was achieved. The efficiency of MSNsPCOL/CG-FA ranked in this order: HCT116 (colon cancer) > HepG2 (liver cancer) > PC3 (prostate cancer). MSNsPCOL/CG-FA exhibited low cytotoxicity (4%) compared to COL (similar to 60%) in BJ1 normal cells. The mechanism of action was studied in detail for HCT116 cells and found to be primarily intrinsic apoptosis caused by an enhanced antimitotic effect. Furthermore, a contribution of genetic regulation (metastasis-associated lung adenocarcinoma transcript 1 (MALAT 1), and microRNA (mir-205)) and immunotherapy effects (angiopoietin-2 (Ang-2 protein) and programmed cell death protein 1 (PD-1) was found. Therefore, this study shows enhanced anticancer effects and reduced cytotoxicity of COL with targeted delivery compared to free COL and is a novel method of developing cancer immunotherapy using a low-cost small-molecule natural prodrug.