International Journal of Nanomedicine (Dec 2018)
Folic acid-nanoscale gadolinium-porphyrin metal-organic frameworks: fluorescence and magnetic resonance dual-modality imaging and photodynamic therapy in hepatocellular carcinoma
Abstract
Yang Chen,1,2,* Wei Liu,3,4,* Yue Shang,1,2 Peipei Cao,1,2 Jianlin Cui,1,2 Zongjin Li,1 Xuebo Yin,3 Yuhao Li1,2 1Nankai University School of Medicine, Tianjin, China; 2Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Medical International Collaborative Innovation Center, Nankai University, Tianjin, China; 3State Key Laboratory of Medicinal Chemical Biology and Tianjin Key Laboratory of Biosensing and Molecular Recognition, College of Chemistry, Nankai University, Tianjin, China; 4School of Science, Tianjin University, Tianjin, China *These authors contributed equally to this work Background: Hepatocellular carcinoma (HCC) is the most common primary liver cancer and severely threatens human health. Since the prognosis of advanced HCC remains poor, there is an urgent need to develop new therapeutic approaches. Porphyrin metal-organic frameworks are a class of porous organic-inorganic hybrid functional materials with good biocompatibility. Methods: Gadolinium-porphyrin metal-organic frameworks were used as a skeleton for folic acid (FA) conjugation to synthesize a novel type of nanoparticle, denoted as folic acid-nanoscale gadolinium-porphyrin metal-organic frameworks (FA-NPMOFs). The FA-NPMOFs were characterized using transmission electron microscopy, Fourier transform infrared spectroscopy and thermogravimetric-differential thermal analysis. The biotoxicity and imaging capability of the FA-NPMOFs were determined using HepG2 cells and embryonic and larval zebrafish. The delivery and photodynamic therapeutic effect of FA-NPMOFs were explored in transgenic zebrafish with doxycycline-induced HCC. Results: FA-NPMOFs were spherical in structure with good dispersion and water solubility. They showed low biotoxicity, emitted bright red fluorescence, and exhibited an excellent magnetic resonance imaging capability, both in vitro and in vivo. Meanwhile, the FA-NPMOFs exhibited a strong affinity for folate receptor (FR)-expressing cells and were delivered to the tumor site in a targeted manner. Moreover, HCC tumor cells were eliminated following laser irradiation. Conclusion: FA-NPMOFs can be used for dual-modality imaging and photodynamic therapy in HCC and show promise for use as a carrier in new therapies for HCC and other FR-positive tumors. Keywords: nanoscale gadolinium-porphyrin metal-organic frameworks, folic acid, hepatocellular carcinoma, dual-modality imaging, photodynamic therapy
