1. Department of Otorhinolaryngology Head and Neck Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China.
2. Department of Joint Surgery, The Affiliated Ganzhou Hospital of Nanchang University, Ganzhou, 341000, China.
3. Department of Otolaryngology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China.
4. Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering,Jinan University, Guangzhou, 510632, China.
*Co-first authors with equal contributions to this work.
The majority of patients diagnosed with nasopharyngeal carcinoma (NPC) present with advanced-stage disease. The main treatment for these patients is concurrent chemoradiotherapy, which has various side effects. To improve the therapeutic effects and reduce the side effects of NPC chemoradiotherapy, we constructed a multifunctional folic acid (FA)-targeted magnetic nanocomposite codelivering tissue factor pathway inhibitor-2 (TFPI-2) and cisplatin (CDDP). This novel nanocomposite (FA-MNP/CDDP/TFPI-2) was obtained by amidation and electrostatic adsorption between FA-methoxypolyethylene glycol-polyethyleneimine (FA-MPEG-PEI) containing the TFPI-2 plasmid and magnetic nanoparticles modified by aldehyde sodium alginate loaded with CDDP. Transmission electron microscopy (TEM) images showed that the size of the individual magnetite particle core was approximately 11.5 nm. The structure and composition of the nanocomposites were identified and examined by 1H nuclear magnetic resonance (NMR) spectroscopy and ultraviolet (UV) spectrophotometry. The fluorescence analysis, Prussian blue iron staining, magnetic resonance (MR) imaging and whole-body fluorescence imaging results demonstrated that FA-MNP/CDDP/TFPI-2 showed high gene transfection efficiency and could target tumor cells via folate receptor (FR)-mediated delivery. The codelivery analysis showed that the obtained FA-MNP/CDDP/TFPI-2 composite could cause significantly more apoptosis than treatment with CDDP or TFPI-2 alone. The results showed that the FA-MNP/CDDP/TFPI-2 composites were successfully synthesized and indicated to be a specific molecular target for the FR with significant inhibitory effects on the growth of HNE-1 cells.
Keywords: magnetic nanoparticles, folate acid, TFPI-2, cisplatin, nasopharyngeal carcinoma, targeted delivery