Synergistic antitumor effect of folate-targeted Pluronic™ F-127/poly(lactic acid) polymersomes for codelivery of doxorubicin and paclitaxel

Plain language summaryHydrophilic doxorubicin hydrochloride (DOX) and hydrophobic paclitaxel (PTX) are two well-known anticancer drugs. Coadministration of DOX and PTX as a free drug cocktail has been widely used in clinical treatment to further improve their anticancer effect. However, this free drug cocktail often causes a lot of side effects such as cardiotoxicity and nephrotoxicity. In order to reduce the side effects of the drug cocktail and enhance their targeted delivery, folic acid-targeted Pluronic (TM) F-127 / poly(lactic acid) (FA-F127-PLA) polymersomes were used to load the drug cocktail. Both the cytotoxicity and cellular uptake data showed that PTX/DOX coloaded FA-F127-PLA polymersomes had better synergistic anticancer ability than a DOX and PTX free-drug cocktail. Tweetable abstractBetter synergistic anticancer effect of doxorubicin hydrochloride and paclitaxel drug cocktail was achieved by codelivering them via folate-targeted Pluronic (TM) F-127 / poly(lactic acid) polymersomes. Aim: Folate-targeted Pluronic (TM) F-127/poly(lactic acid) (FA-F127-PLA) polymersomes were used as codelivery carriers of doxorubicin hydrochloride (DOX) and paclitaxel (PTX) to achieve a targeted synergistic antitumor effect. Materials & methods: The cytotoxicity of PTX/DOX polymersomes against OVCAR-3 cells was determined by methyl thiazolyl tetrazolium assay. The cellular uptake of PTX/DOX polymersomes was examined by HPLC and micro-bicinchoninic acid techniques. Results: The polymersomes showed a bilayer core-shell structure with negative charge and good dispersion. PTX1/DOX5 polymersomes with a mass ratio of PTX to DOX of 1:5 showed the best synergistic effect and the highest cellular uptake. Conclusion: FA-F127-PLA polymersomes have the great promise for codelivery of multiple chemotherapeutics to achieve a targeted antitumor synergistic effect.