Irinotecan-loaded ROS-responsive liposomes containing thioether phosphatidylcholine for improving anticancer activity

In this work, irinotecan (IR)-loaded reactive oxygen species (ROS)-responsive liposomes were developed for improving anticancer activity. First of all, thioether phosphatidylcholine (S-PC) based liposomes (S-LP) were prepared via ethanol injection method. After that, IR was actively loaded into liposomes (IR/S-LP) by using sucrose octasulfate triethylamine (TEA8-SOS) with encapsulation efficiency of 97.0 ± 1.0% and loading efficiency of 30.6 ± 0.1%. The IR/S-LP liposomal formulation was further characterized through dynamic light scattering (DLS) and transmission electron microscopy (TEM), confirming regular spherical structure with particle size of 100.2 ± 5.2 nm and zeta potential of −25.1 ± 2.2 mV. Moreover, the IR/S-LP formulation exhibited improved drug release profiles in the presence of H2O2. Cellular uptake behavior of IR/S-LP was observed by using confocal laser scanning microscopy (CLSM). Pharmacokinetic analyses further confirmed that IR/S-LP could lead to extending SN38 exposure. Ultimately, in vivo antitumor test in 4T-1 tumor-bearing mice revealed that IR/S-LP had dose-dependent tumor growth inhibition and superior anticancer activity compared to free IR and convenient IR-liposomes (Onivyde®-like) ascribed to ROS-responsiveness and raised bioavailability. Taken together, IR loaded S-PC based liposomes have ROS responsiveness leading to enhanced anticancer activity, which might be an alternative of convenient IR-liposomes.