CD-44 active cystamine-bridged hyaluronic acid-polydopamine nanoparticles for chemo-photothermal cancer therapy

The development of targeted drug delivery systems for cancer treatment has been a topic of great interest in recent years. We developed redox-responsive, NIR-activated, cystamine-bridged hyaluronan-polydopamine (Cys-HA-PDA) nanoparticles (NPs) loaded with doxorubicin (Dox) that bind to CD44 receptors on cancer cells and exhibit enhanced anticancer efficacy due to a chemo-photothermal effect under redox conditions. Synthesized Cys-HA-PDA NPs at 200 µg/ml concentration produced a temperature of 59.5℃ at 2 W/cm2, which destroyed tumor cells. The presence of disulfide bonds in Cys-HA-PDA NPs resulted in self-degradability in the cytosol of cancer cells. Furthermore, electrostatic interactions and pi-pi stacking allowed Dox to be successfully encapsulated in Cys-HA-PDA nanoparticles; calculated maximum drug loading and encapsulation efficiency were 21.6% and 88.3%, respectively. The anticancer activity of Dox-loaded NPs on HepG2 cancer cells was increased under NIR laser light (800 nm, 2 W/cm2). Furthermore, interaction with CD44 receptor enhanced the intracellular uptake of Dox-loaded Cys-HA-PDA NPs by HepG2 cells. Overall, the study shows that the use of redox-responsive nanoparticles for CD44-targeted drug delivery is a promising anticancer strategy.