Folic acid-modified ROS-responsive nanoparticles encapsulating luteolin for targeted breast cancer treatment

Luteolin (Lut) is a natural flavonoid polyphenolic compound with multiple pharmacological activities, such as anti-oxidant, anti-inflammatory, and anti-tumor effects. However, the poor aqueous solubility and low bioactivity of Lut restrict its clinical translation. Herein, we developed a reactive oxygen species (ROS)-responsive nanoplatforms to improve the bioactivity of Lut. Folic acid (FA) was employed to decorate the nanoparticles (NPs) to enhance its targeting ability. The size of Lut-loaded ROS-responsive nanoparticles (Lut/Oxi-alpha CD NPs) and FA-modified Lut/Oxi-alpha CD NPs (Lut/FA-Oxi-alpha CD NPs) is 210.5 +/- 6.1 and 196.7 +/- 1.8 nm, respectively. Both Lut/Oxi-alpha CD NPs and Lut/FA-Oxi-alpha CD NPs have high drug loading (14.83 +/- 3.50 and 16.37 +/- 1.47%, respectively). In vitro cellular assays verified that these NPs could be efficiently internalized by 4T1 cells and the released Lut from NPs could inhibit tumor cells proliferation significantly. Animal experiments demonstrated that Lut/Oxi-alpha CD NPs, especially Lut/FA-Oxi-alpha CD NPs obviously accumulated at tumor sites, and inhibited tumor growth similar to 3 times compared to the Lut group. In conclusion, the antitumor efficacy of Lut was dramatically improved by targeting delivery with the ROS-responsive nanoplatforms.

Automated summary

The bioactivity of Luteolin has been enhanced through the development of ROS-responsive nanoplatforms with folate decoration, leading to efficient internalization by cancer cells and significant inhibition of tumor cell proliferation in vitro. Animal experiments demonstrated that these nanoparticles accumulated at tumor sites and inhibited tumor growth 3 times more effectively than the control group, showcasing the promising potential of targeted delivery for improving the antitumor efficacy of Luteolin.