Non-ionic polysorbate-based nanoparticles for efficient combination chemo/photothermal/photodynamic therapy

Abstract

Combination therapy has gained great attraction as an effective strategy for the treatment of cancers. In this study, non-ionic polysorbate-based nanoparticles were prepared for combination chemo/photothermal/photodynamic cancer therapy via effective intracellular delivery of piperlongumine (PL) and indocyanine green (ICG). PL was used as a pro-oxidant drug that can induce selective apoptosis through the increase of oxidative stress in cancer cells. ICG was used as a near-infrared (NIR) light-absorbing photothermal and photodynamic agent. Non-ionic Tween 80 (T80) polysorbate was used to prepare PL- and ICG-loaded micelles with nanoscale diameters. Both PL and ICG were efficiently encapsulated in the T80-based micelles. Storage stability of ICG in aqueous solutions was greatly improved by encapsulation into the T80-based micelles. ICG-loaded T80 micelles (ICG-T80) showed higher photothermal conversion efficiency than free ICG. T80 also increased cellular uptake of ICG. Moreover, ICG-T80 showed NIR light-triggered reactive oxygen species (ROS) generation in MCF-7 human breast cancer cells, owing to the photodynamic effects of NIR light-absorbing ICG. PL-loaded T80 micelles also increased intracellular ROS levels in MCF-7 cells owing to the pro-oxidant activity of PL. In vitro study showed that ICG-T80 micelles exhibited efficient anticancer activity under NIR irradiation via combined photothermal therapy (PTT) and photodynamic therapy (PDT). PL- and ICG-loaded T80 micelles (PL-ICG-T80) further increased the cytotoxicity via combined chemo/PTT/PDT. PL-ICG-T80 also showed cancer-selective cytotoxicity. This study demonstrates that PL-ICG-T80 micelles are effective for NIR light-triggered combination chemo/PTT/PDT.