A Tf-modified tripterine-loaded coix seed oil microemulsion enhances anti-cervical cancer treatment

Abstract

Yunyan Chen,1–3 Ding Qu,1,2 Rongping Fu,1,2 Mengfei Guo,1,2 Yue Qin,1,2 Jian Guo,1,2 Yan Chen1,2 1Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, China; 2Research Center for Multicomponent of Traditional Chinese Medicine and Microecology, Jiangsu Provincial Academy of Traditional Chinese Medicine, Nanjing 210028, China; 3Wannan Medical College, Wuhu 241002, China Purpose: A transferrin-modified microemulsion carrying coix seed oil and tripterine (Tf-CT-MEs) was developed for improved tumor-specific accumulation and penetration to enhance cervical cancer treatment. Materials and methods: Tripterine-loaded coix seed oil microemulsion (CT-MEs) was prepared through one-step emulsion method. The morphology, size, and zeta potential of CT-MEs and Tf-CT-MEs were examined by transmission electron microscopy and dynamic light scattering. The cellular uptake and mechanisms of HeLa cells were investigated by flow cytometry. Intratumor penetration was investigated using a HeLa three-dimensional (3D) tumor spheroid as the model. The cytotoxicity of the CT-MEs and Tf-CT-MEs against HeLa cells were evaluated by the MTT assay. Additionally, the apoptotic rate of CT-MEs and Tf-CT-MEs inducing apoptosis in HeLa cells was evaluated. Results: In the physicochemical characterization, coix seed oil and CT-MEs exhibited a small size (32.47±0.15 nm) and nearly neutral surface charge (-0.36±0.11 mV). After modification with transferrin, the particle size of Tf-CT-MEs slightly increased to 40.02±0.21 nm, but the zeta potential decreased remarkably to -13.63±1.31 mV. The IC50 of Tf-CT-MEs against HeLa cells was 0.7260 µM, which was 2.58-fold lower than that of CT-MEs. In cellular studies, the intracellular fluorescence intensity of fluorescein isothiocyanate (FITC)-labeled Tf-CT-MEs (FITC/Tf-CT-MEs) was 2.28-fold higher than that of FITC-labeled CT-MEs (FITC/CT-MEs). The fluorescence signal of Tf-CT-MEs was observed at 350 µm below the surface of the 3D tumor spheroid. The apoptotic rate of cells treated with Tf-CT-MEs was 1.73- and 2.77-fold higher than that of cells treated with CT-MEs and tripterine, respectively, which was associated with mitochondrial-targeted delivery of tripterine. Moreover, Tf-CT-MEs was capable of significantly downregulating the cellular level of antiapoptotic proteins and arrested cell proliferation in the G2/M phase. Conclusion: Taken together, Tf-CT-MEs holds promising potential to be an efficient drug delivery system for combinational therapy of cervical cancer. Keywords: tripterine, coix seed oil, microemulsion, deep penetration, anti-cervical cancer

Keywords

• tripterine
• coix seed oil
• microemulsion
• deep penetration
• anti-cervical cancer