%0 Journal Article
%T Codelivery of dihydroartemisinin and doxorubicin in mannosylated liposomes for drug-resistant colon cancer therapy
%A Ai-hua Wu
%A Bin-fan Chen
%A Hui-ge Peng
%A Hui-yuan Wang
%A Wen-yuan Zhang
%A Xue-jia Kang
%A Yong-zhuo Huang
%J Archive of "Acta Pharmacologica Sinica".
%D 2017
%R 10.1038/aps.2017.10
%X 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 (Man-liposomes). 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 ¦Ìg/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 Man-liposomes involved preferential nuclear accumulation of the therapeutic agents, enhanced cancer cell apoptosis, downregulation of Bcl-xl, and the induction of autophagy
%K human colon cancer
%K multidrug resistance
%K doxorubicin
%K dihydroartemisinin
%K combination therapy
%K tumor-targeted delivery
%K mannosylated liposome
%K mannose receptor
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520183/