@article{APS9617,
author = {Xue-jia KANG and Hui-yuan WANG and Hui-ge PENG and Bin-fan CHEN and Wen-yuan ZHANG and Ai-hua WU and Qin XU and Yong-zhuo HUANG},
title = {Codelivery of dihydroartemisinin and doxorubicin in mannosylated liposomes for drug-resistant colon cancer therapy},
journal = {Acta Pharmacologica Sinica},
volume = {38},
number = {6},
year = {2017},
keywords = {},
abstract = {Multidrug resistance (MDR) is a major hurdle in cancer chemotherapy and makes the treatment benefits unsustainable. Combination therapy is a commonly used method for overcoming MDR. In this study we investigated the anti-MDR effect of dihydroartemisinin (DHA), a derivative of artemisinin, in combination with doxorubicin (Dox) in drug-resistant human colon tumor HCT8/ADR cells. We developed a tumor-targeting codelivery system, in which the two drugs were co-encapsulated into the mannosylated liposomes (Manliposomes). The Man-liposomes had a mean diameter of 158.8 nm and zeta potential of -15.8 mV. In the HCT8/ADR cells that overexpress the mannose receptors, the Man-liposomes altered the intracellular distribution of Dox, resulting in a high accumulation of Dox in the nuclei and thus displaying the highest cytotoxicity (IC50=0.073 μg/mL) among all the groups. In a subcutaneous HCT8/ADR tumor xenograft model, administration of the Man-liposomes resulted in a tumor inhibition rate of 88.59%, compared to that of 47.46% or 70.54%, respectively, for the treatment with free Dox or free Dox+DHA. The mechanisms underlying the anti-MDR effect of the Manliposomes involved preferential nuclear accumulation of the therapeutic agents, enhanced cancer cell apoptosis, downregulation of Bcl-xl, and the induction of autophagy.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/9617}
}