Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar (M.P.), India.
J Drug Target. 2012 May;20(4):372-80. doi: 10.3109/1061186X.2012.662687. Epub 2012 Feb 18.
In the present study attempt has been made to enhance the selective tumor cell killing in mouse xenograft model using DQAsomes as a mitochondriotropic carrier and transferrin (Tf) as a ligand to target tumor cells.
Tf modified DQAsomes (Tf-DQAsomes) were prepared by incubating preformed paclitaxel loaded DQAsomes with Tf in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride. Developed systems were characterized for size and size distribution, entrapment efficiency, and in vitro drug release. Fluorescence microscopy and flow cytometry were performed to evaluate cellular uptake of the carriers. Antitumor activity was determined using HeLa cells. In vivo therapeutic efficacy was determined in xenograft mouse model.
Uptake studies demonstrated that Tf-DQAsomes result in higher fluorescence intensity to the cancer cells as compared to plain DQAsomes. Tf-DQAsomes exhibited better antitumor activity in vitro as compared to plain DQAsomes and paclitaxel solution. In vivo biodistribution study revealed that paclitaxel concentration in the tumor was much higher in the case of Tf-DQAsomes as compared to plain DQAsomes and paclitaxel solution; however in other organs it was much lower than the latter two formulations. Tf-DQAsomes exhibited significant antitumor activity in the mouse xenograft model.
The finding demonstrated that Tf conjugated DQAsomes can effectively be delivered to the tumor in vivo and exhibit significant antitumor activity.
本研究试图通过 DQAsomes 作为靶向肿瘤细胞的线粒体载体和转铁蛋白（Tf）作为配体，增强小鼠异种移植模型中肿瘤细胞的选择性杀伤。
Tf 修饰的 DQAsomes（Tf-DQAsomes）是通过在 1-乙基-3-（3-二甲基氨基丙基）碳二亚胺盐酸盐存在下，将预形成的紫杉醇负载的 DQAsomes 与 Tf 孵育来制备的。对开发的系统进行了大小和粒径分布、包封效率和体外药物释放的特性研究。荧光显微镜和流式细胞术用于评估载体的细胞摄取。使用 HeLa 细胞测定抗肿瘤活性。在异种移植小鼠模型中测定体内治疗效果。
摄取研究表明，与普通 DQAsomes 相比，Tf-DQAsomes 导致癌细胞的荧光强度更高。与普通 DQAsomes 和紫杉醇溶液相比，Tf-DQAsomes 表现出更好的体外抗肿瘤活性。体内生物分布研究表明，与普通 DQAsomes 和紫杉醇溶液相比，Tf-DQAsomes 使肿瘤中的紫杉醇浓度更高;然而，在其他器官中，其浓度远低于后两种制剂。Tf-DQAsomes 在小鼠异种移植模型中表现出显著的抗肿瘤活性。
研究结果表明，Tf 缀合的 DQAsomes 可以有效地递送到体内肿瘤，并表现出显著的抗肿瘤活性。
