论文部分内容阅读
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.