Codelivery of doxorubicin and MDR1-siRNA by mesoporous silica nanoparticles-polymerpolyethylenimine to improve oral squamous carcinoma treatment.
Codelivery of doxorubicin and MDR1-siRNA by mesoporous silica nanoparticles-polymerpolyethylenimine to improve oral squamous carcinoma treatment.
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介孔二氧化硅纳米颗粒-聚合物聚乙烯亚胺共同递送阿霉素和 MDR1-siRNA 以改善口腔鳞状细胞癌的治疗
DOI：
10.2147/ijn.s150610
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发表时间：
2018
影响因子：
8
通讯作者：
Sun H
中科院分区：
文献类型：
--
作者：
Wang D;Xu X;Zhang K;Sun B;Wang L;Meng L;Liu Q;Zheng C;Yang B;Sun H
口腔癌是一种头颈部癌症，在全球最常见的癌症中排名第七，在最常见的死亡原因中排名第九。约90%的口腔癌是鳞状细胞癌。手术和放疗加化疗和不加化疗是口腔癌的主要治疗方法。仍然需要更好的高级治疗。多药耐药是口腔癌化疗失败的重要原因。在这项研究中，我们试图构建一种新型的纳米粒子，它可以携带mdr1-siRNA来阻断mdr1的表达，并将化疗药物阿霉素(DOX)带入癌细胞，以直接杀死肿瘤细胞，而几乎没有多药耐药的作用。结果表明，阳离子聚合物聚乙烯亚胺(PEI)可以修饰介孔二氧化硅纳米颗粒(MSNP)，使其表面带正电荷，从而使MSNP能够携带MDR1-siRNA和DOX。转染率分析表明，MSNP-PEI-DOX/mdr1-siRNA在体外能有效地转入KBV细胞。转导msNP-PEI-DOX/mdr1-siRNA的KBV细胞在体外能有效地降低MDR1基因的表达(72h后上调约70%)，并诱导KBV细胞发生凋亡(48h后达24.27%)。重要的是，MSNP-PEI-DOX/mdr1-siRNA显著缩小了肿瘤体积(治疗后28天后缩小了81.64%)，并减缓了体内肿瘤生长速度(P<；0.05)。综上所述，新合成的MSNP-PEI-DOX/MDR1-siRNA在治疗多药耐药癌症方面比单纯DOX提高了癌症化疗效果，清楚地表明MSNP-PEI-DOX/MDR1-siRNA在未来的多药耐药癌症治疗中具有潜在的应用前景。
Oral cancer is a type of head and neck cancer that is the seventh most frequent cancer and the ninth most frequent cause of death globally. About 90% of oral cancer is of squamous cell carcinoma type. Surgery and radiation with and without chemotherapy are the major treatments for oral cancer. Better advanced treatment is still needed. Multidrug resistance plays an important role in failure of oral cancer chemotherapy. In this study, we tried to fabricate a novel nanoparticle that could carry both MDR1-siRNA to block MDR1 expression and doxorubicin (DOX), a chemotherapy drug, into cancer cells in order to directly kill the cells with little or no effect of multidrug resistance. Results showed that mesoporous silica nanoparticles (MSNP) can be modified by cationic polymerpolyethylenimine (PEI) to obtain positive charges on the surface, which could enable the MSNP to carry MDR1-siRNA and DOX. The transfection efficiency assays demonstrated that the MSNP-PEI-DOX/ MDR1-siRNA was efficiently transfected into KBV cells in vitro. KBV cells transfected with MSNP-PEI-DOX/MDR1-siRNA could effectively decrease gene expression of MDR1 (~70% increase after 72 hours posttreatment) and induce the apoptosis of KBV cells (24.27% after 48 hours posttreatment) in vitro. Importantly, MSNP-PEI-DOX/MDR1-siRNA dramatically reduced the tumor size (81.64% decrease after 28 days posttreatment) and slowed down tumor growth rate compared to the control group in vivo (P<0.05). In the aggregate, newly synthesized MSNP-PEI-DOX/MDR1-siRNA improves cancer chemotherapy effect in terms of treating multidrug-resistant cancer compared to DOX only, clearly demonstrating that MSNP-PEI-DOX/MDR1-siRNA has potential therapeutic application for multidrug-resistant cancer in the future.