HIF1 alpha-siRNA and gemcitabine combination-based GE-11 peptide antibody-targeted nanomedicine for enhanced therapeutic efficacy in pancreatic cancers
HIF1 alpha-siRNA and gemcitabine combination-based GE-11 peptide antibody-targeted nanomedicine for enhanced therapeutic efficacy in pancreatic cancers
复制标题
基于 HIF1 α-siRNA 和吉西他滨组合的 GE-11 肽抗体靶向纳米药物可增强胰腺癌的治疗效果
DOI：
10.1080/1061186x.2018.1552276
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发表时间：
2019
影响因子：
4.5
通讯作者：
He Songqing
中科院分区：
文献类型：
--
作者：
Lin Chengjie;Hu Zhigao;Yuan Gu;ou;Su Huizhao;Zeng Yonglian;Guo Zhenya;Zhong Fudi;Jiang Keqing;He Songqing
胰腺癌是世界上最致命的癌症之一，平均5年生存率不到6%。本研究成功制备了吉西他滨（GEM）和HIF1α-siRNA负载GE-11肽偶联脂质体，并对其在胰腺癌细胞中的抗肿瘤作用进行了评价。GE11增加了脂质体载体的靶向特异性，增加了癌细胞内的浓度。此外，GEM与HIF1a-siRNA协同组合对癌细胞增殖的下降有显著的改善作用。siRNA能有效降低HIF1a基因在癌细胞中的表达。重要的是，GE-11肽偶联的GEM/siRNA负载脂质体（GE-GML/siRNA）增加了凋亡细胞的总量，并且处于凋亡晚期的细胞比例更高。GE-GML显著诱导癌细胞凋亡，并诱导染色质凝聚和细胞核断裂，这被认为是细胞凋亡和死亡的典型特征。GE-GML/siRNA显示肿瘤负荷显著减少，表明该制剂具有优越的抗癌功效。与对照组相比，GE-GML/siRNA的肿瘤减少了4倍，与GE-GML相比，分别减少了2倍。总的来说，目前的工作为GEM和HIF1a-siRNA在靶向纳米载体系统中的结合作为胰腺癌治疗的独特治疗选择奠定了基础。
Pancreatic cancer is one of the deadliest cancers across the world with an average 5-year survival rate of less than <6%. In this study, gemcitabine (GEM) and HIF1α-siRNA loaded GE-11 peptide conjugated liposome was successfully prepared and evaluated for its antitumor efficacy in pancreatic cancer cells. The GE11 increased the targeting specificity of liposome carrier and increased the intracellular concentrations in the cancer cells. Furthermore, synergistic combination of GEM and HIF1a-siRNA exhibited remarkable improvement in the declining of cancer cell proliferations. siRNA could effectively decrease the expression of HIF1a gene in the cancer cells. Importantly, GE-11 peptide-conjugated GEM/siRNA-loaded liposomes (GE-GML/siRNA) increased the total amount of apoptosis cells with higher proportion of cells in late apoptosis phase. GE-GML induced remarkable apoptosis of cancer cells and induced chromatin condensation and nuclear fragmentation which are considered to be typical features of apoptosis and cell death. GE-GML/siRNA showed a significant reduction in the tumour burden suggesting the superior anticancer efficacy of this formulation. GE-GML/siRNA showed four-fold reduction in tumour compared to control and two-fold reduction compared to GE-GML, respectively. Overall, present work lays foundation for the combination of GEM and HIF1a-siRNA loaded in a targeted nanocarrier system as a unique therapeutic option in pancreatic cancer treatment.