Found programs: Natural Science Research Project of Anhui Educational Committee(No.2023AH040370);Anhui Medical University Research Level Enhancement Plan(No.2021xkjT015)
Authors:Rong Jing; Liu Tongtong; Yin Xiujuan; Zhang Lei; Wang Xiao
Keywords:magnetic resonance imaging;lipid nanoparticles;hepatocellular carcinoma;molecular targeted therapy;lactobionic acid;miR-145;camptothecin;combination therapy
DOI:10.19405/j.cnki.issn1000-1492.2024.09.002
〔Abstract〕 Objective To develop liver cancer-targeted nanoparticles(LA-CMGL) co-loaded with miR-145/camptothecin(CPT) and assess their targeting specificity, combined anti-tumor effects, and magnetic resonance imaging efficacy. Methods Laser scanning confocal microscopy and flow cytometry were utilized to evaluate the targeted uptake of lactobionic acid-modified and unmodified nanoparticles by HepG2 cells and HepaRG cells; quantitative polymerase chain reaction(qPCR) was employed to assess miR-145 content in tumor cells and tissues. The cytotoxicity of CPT, LA-CPT-LNPs and LA-CMGL on HepG2 cells were assessed using the CCK-8 assay. qPCR was also used to evaluate the effect of CPT, LA-CPT-LNPs and LA-CMGL on apoptosis of HepG2 cells. MRI was performed to measure the relaxation rate of LA-CMGL and evaluate its targeting imaging effect on liver cancer cells. Results The uptake rate of LA-CMGL by HepG2 cells surpassed that of CMGL significantly. The relative miR-145 content in liver cancer cells and mouse liver cancer tissues in the LA-CMGL group was markedly higher compared to free miR-145 and CMGL groups(P<0.001). The apoptosis rate of HepG2 cells in the LA-CMGL group exceeded that in the CMGL group and CPT group(P<0.01). At the same Gd3+concentration, the relaxation rate of LA-CMGL significantly surpassed that of Gd-DOTA, and the MRI signal of LA-CMGL in HepG2 cells markedly increased compared to CMGL and Gd-DOTA. Conclusion LA-CMGL exhibits promising liver cancer-targeted delivery, combined anti-tumor effects, and MRI liver cancer cell-targeted imaging, offering a novel avenue for combined drug/gene therapy for liver cancer.