关键词： ALT, alanine transaminase AST, aspartate transaminase AUC, area under the curve BUN, blood urea nitrogen CHO, cholesterol CO2, carbon dioxide CR, creatinine Combination therapy Cu2+, copper ions DL, drug loading DLS, dynamic light scattering DMSO, dimethyl sulfoxide DNA, deoxyribonucleic acid DOX, doxorubicin DSPE-PEG2000, 2-distearoyl-snglycero-3-phosphoethanolamine-N-[methyl(polyethylene glycol)-2000 DTT, d,l-dithiothreitol EDTA, ethylene diamine tetraacetic acid EE, encapsulation efficacy FBS, fetal bovine serum GSH, glutathione H&E, hematoxylin and eosin H2O2, hydrogen peroxide HEPES, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid HPLC, high-performance liquid chromatography HSPC, hydrogenated soybean phospholipids IC50, half maximal inhibitory concentration IVIS, in vivo imaging system MLVs, multilamellar vesicles MRT, mean residence time MTD, maximum tolerated dose MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Nanoparticles PBS, phosphate buffer saline PDI, polydispersity index PSD LPs, PTX-S-DOX liposomes PSD NPs, PTX-S-DOX self-assembled nanoparticles PSD, PTX-S-DOX PTX, paclitaxel Paclitaxel–doxorubicin prodrug Prodrug ROS, reactive oxygen species Remote loading liposomes SD, standard deviation Safety TEM, transmission electron microscopy UV, ultraviolet

来  源：   DOI：10.1016/j.apsb.2020.04.011   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
The combination of paclitaxel (PTX) and doxorubicin (DOX) has been widely used in the clinic. However, it remains unsatisfied due to the generation of severe toxicity. Previously, we have successfully synthesized a prodrug PTX-S-DOX (PSD). The prodrug displayed comparable in vitro cytotoxicity compared with the mixture of free PTX and DOX. Thus, we speculated that it could be promising to improve the anti-cancer effect and reduce adverse effects by improving the pharmacokinetics behavior of PSD and enhancing tumor accumulation. Due to the fact that copper ions (Cu2+) could coordinate with the anthracene nucleus of DOX, we speculate that the prodrug PSD could be actively loaded into liposomes by Cu2+ gradient. Hence, we designed a remote loading liposomal formulation of PSD (PSD LPs) for combination chemotherapy. The prepared PSD LPs displayed extended blood circulation, improved tumor accumulation, and more significant anti-tumor efficacy compared with PSD NPs. Furthermore, PSD LPs exhibited reduced cardiotoxicity and kidney damage compared with the physical mixture of Taxol and Doxil, indicating better safety. Therefore, this novel nano-platform provides a strategy to deliver doxorubicin with other poorly soluble antineoplastic drugs for combination therapy with high efficacy and low toxicity.
摘要：
暂无翻译
公众号