International Journal of Nanomedicine (Apr 2023)
Luteolin-Loaded Nanoparticles for the Treatment of Melanoma
Abstract
Qiao-Ting Fu,1,* Xiao-Qin Zhong,1,* Mei-Yu Chen,1,* Jia-Yi Gu,2 Jian Zhao,3 De-Hong Yu,4 Fei Tan1,5 1Shanghai Skin Disease Clinical College, The Fifth Clinical Medical College, Anhui Medical University, Shanghai Skin Disease Hospital, Shanghai, 200443, People’s Republic of China; 2Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200011, People’s Republic of China; 3Department of Oncology-Pathology, Karolinska Institutet, BioClinicum, Karolinska University Hospital Solna, Solna, Sweden; 4Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, 200444, People’s Republic of China; 5Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, 200443, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei Tan; Dehong Yu, Email [email protected]; [email protected] and Purpose: Luteolin (LUT), a flavonoid found in various plants, has been reported to have potential therapeutic effects in melanoma. However, poor water solubility and low bioactivity have severely restricted the clinical application of LUT. Based on the high reactive oxygen species (ROS) levels in melanoma cells, we developed nanoparticles encapsulating LUT with the ROS-responsive material poly(propylene sulfide)-poly(ethylene glycol) (PPS-PEG) to enhance the water solubility of LUT, accelerate the release of LUT in melanoma cells, and further enhance its anti-melanoma effect, providing a viable solution for the application of LUT nano-delivery systems in melanoma therapy.Methods: In this study, LUT-loaded nanoparticles were prepared with PPS-PEG and named as LUT-PPS-NPs. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were applied to determine the size and morphology of LUT-PPS-NPs. In vitro studies were carried out to determine the uptake and mechanism of LUT-PPS-NPs by SK-MEL-28 melanoma cells. According to the CCK-8 assay, the cytotoxic effects of LUT-PPS-NPs on human skin fibroblasts (HSF) and SK-MEL-28 cells were assessed. Apoptosis assays, cell migration and invasion assays, and proliferation inhibition assays with low and normal density plating were also applied to test the in vitro anti-melanoma effect. Additionally, melanoma models were established utilizing BALB/c nude mice and initially evaluated the growth inhibitory impact following intratumoral injection of LUT-PPS-NPs.Results: The size of LUT-PPS-NPs was 169.77 ± 7.33 nm with high drug loading (15.05 ± 0.07%). In vitro, cellular assays confirmed that LUT-PPS-NPs were efficiently internalized by SK-MEL-28 cells and showed low cytotoxicity against HSF. Moreover, LUT released from LUT-PPS-NPs significantly inhibited tumor cell proliferation, migration and invasion. Animal experiments showed that LUT-PPS-NPs inhibited tumor growth more than 2-fold compared with the LUT group.Conclusion: In conclusion, the LUT-PPS-NPs developed in our study enhanced the anti-melanoma effect of LUT.Keywords: luteolin, melanoma, nanoparticles, PPS-PEG, drug delivery system
