Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Nanchang University, No.1 Minde Road, Nanchang, China.
Department of Emergency, The Second Affiliated Hospital of Nanchang University, No.1 Minde Road, Nanchang, China.
Mater Sci Eng C Mater Biol Appl. 2018 Aug 1;89:328-335. doi: 10.1016/j.msec.2018.04.011. Epub 2018 Apr 11.
In this study, we have developed an antibody fragment (AF)-conjugated gemcitabine (GEM) and paclitaxel (PTX)-loaded liposome (AF-GPL) to enhance the therapeutic efficacy in pancreatic cancer treatment. The maleimide-thiol chemistry was utilized to conjugate AF on the liposome surface. The dual-drug loaded liposome was nanosized and exhibited a controlled release of both the drugs. Importantly, two drugs have different release pattern over a period of time. The AF-conjugated liposome showed enhanced cellular uptake in pancreatic cancer cells compared to that of non-targeted liposome. Two-fold higher internalization of particles might increase the intracellular concentration of anticancer drugs that might further increase the therapeutic efficacy in pancreatic cancer cells. AF-GPL showed significantly higher cytotoxic effect in pancreatic cancer cell compared to that of non-targeted GPL. The IC50 value of GEM, PTX, GPL and AF-GPL were 5.9 μg/ml, 4.2 μg/ml, 1.92 μg/ml, and 0.45 μg/ml, respectively. Consistently, AF-GPL (4.12) showed significantly higher ratio of Bax/Bcl-2 compared to that of non-targeted GPL (2.8). Importantly, AF-GPL induced a significant apoptosis of cancer cells with predominant amount of cells in late apoptosis cells. Overall, AF-conjugated nanosystem could potentially improve the therapeutic efficacy in pancreatic cancers.
在这项研究中，我们开发了一种抗体片段（AF）缀合的吉西他滨（GEM）和紫杉醇（PTX）负载脂质体（AF-GPL），以增强胰腺癌治疗的疗效。利用马来酰亚胺-巯基化学将 AF 缀合到脂质体表面。载双药的脂质体为纳米尺寸，并表现出两种药物的控制释放。重要的是，两种药物在一段时间内具有不同的释放模式。与非靶向脂质体相比，AF 缀合的脂质体在胰腺癌细胞中表现出增强的细胞摄取。颗粒的两倍高的内化可能会增加抗癌药物的细胞内浓度，这可能会进一步提高胰腺癌细胞中的治疗效果。与非靶向 GPL 相比，AF-GPL 在胰腺癌细胞中表现出显著更高的细胞毒性作用。GEM、PTX、GPL 和 AF-GPL 的 IC50 值分别为 5.9μg/ml、4.2μg/ml、1.92μg/ml 和 0.45μg/ml。一致地，AF-GPL（4.12）与非靶向 GPL（2.8）相比，Bax/Bcl-2 的比值显著更高。重要的是，AF-GPL 诱导癌细胞发生明显的凋亡，晚期凋亡细胞中的细胞数量居多。总的来说，AF 缀合的纳米系统有可能提高胰腺癌的治疗效果。
