%0 Journal Article
%T Tf-PEG-PLL-PLGA nanoparticles enhanced chemosensitivity for hypoxia-responsive tumor cells
%A Baoan Chen
%A Fei Wang
%A Guohua Xia
%A HaiXiang Yin
%A Haijun Zhang
%A Liting Guo
%A Ping Liu
%A Xue Wu
%A Xueming Li
%A Yonglu Wang
%J Archive of "OncoTargets and therapy".
%D 2016
%R 10.2147/OTT.S108169
%X Hypoxia is an inseparable component of the solid tumor as well as the bone marrow microenvironment. In this study, we investigated the effect of the novel polyethylene glycol (PEG)-poly L-lysine (PLL)-poly lactic-co-glycolic acid (PLGA) based nanoparticles (NPs) modified by transferrin (Tf) loaded with daunorubicin (DNR) (DNR-Tf-PEG-PLL-PLGA-NPs, abbreviated as DNR-Tf-NPs) on leukemia cells (K562) under hypoxia. In vitro and in vivo tests to determine the effect of the enhanced chemosensitivity were evaluated using the immunofluorescence, flow cytometry, 3,-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-tetrazoliumbromide assay, Western blot analysis, histopathological examination, and immunohistochemistry analysis. Under hypoxia, K562 cells were hypoxia-responsive with the inhibitory concentration 50% (IC50) of DNR increased, resulting in chemotherapy insensitivity. By targeting the transferrin receptor (TfR) on the surface of K562 cells, DNR-Tf-NPs led to an increased intracellular DNR level, enhancing drug sensitivity of K562 cells to DNR with a decreased IC50, even under hypoxia. We further detected the protein levels of hypoxia-inducible factor-1¦Á (HIF-1¦Á), Bcl-2, Bax, and caspase-3 in K562 cells. The results indicated that DNR-Tf-NPs downregulated HIF-1¦Á and induced apoptosis to overcome hypoxia. In the xenograft model, injection of DNR-Tf-NPs significantly suppressed tumor growth, and the immunosignals of Ki67 in DNR-Tf-NPs group was significantly lower than the other groups. It was therefore concluded that DNR-Tf-NPs could be a promising candidate for enhancing drug sensitivity under hypoxia in tumor treatment
%K hypoxia
%K PEG-PLL-PLGA nanoparticles
%K transferrin receptor
%K chemosensitivity
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990384/