International Journal of Nanomedicine (Mar 2022)
Fluorescent Imaging-Guided Chemo- and Photodynamic Therapy of Hepatocellular Carcinoma with HCPT@NMOFs-RGD Nanocomposites
Abstract
Yue Shang,1,* Hui Zhang,2,* Yajia Cheng,3 Peipei Cao,3 Jianlin Cui,3 Xuebo Yin,4 Saijun Fan,1 Yuhao Li5 1Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, People’s Republic of China; 2Shanghai Institute of Quality Inspection and Technical Research, Shanghai, People’s Republic of China; 3Department of Pathology, Nankai University School of Medicine, Tianjin, People’s Republic of China; 4College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, People’s Republic of China; 5Beijing Geriatric Medical Research Center, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuhao Li, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China, Tel +86-10-83198269, Email [email protected]: Hepatocellular carcinoma (HCC), arising from hepatocytes, is the most common primary liver cancer. It is urgent to develop novel therapeutic approaches to improve the grim prognosis of advanced HCC. 10-hydroxycamptothecin (HCPT) has good antitumor activity in cells; however, its hydrophobicity limits its application in the chemotherapy of HCC. Recently, nanoscale porphyrin metal-organic frameworks have been used as drug carriers due to their low biotoxicity and photodynamic properties.Methods: Nanoscale zirconium porphyrin metal-organic frameworks (NMOFs) were coated with arginine-glycine-aspartic acid (RGD) peptide to prepare NMOFs-RGD first. The HepG2 cell line, zebrafish embryos and larvae were used to test the biotoxicity and fluorescence imaging capability of NMOFs-RGD both in vitro and in vivo. Then, NMOFs were used as the skeleton, HCPT was assembled into the pores of NMOFs, while RGD peptide was wrapped around to synthesize a novel kind of nanocomposites, HCPT@NMOFs-RGD. The tissue distribution and chemo- and photodynamic therapeutic effects of HCPT@NMOFs-RGD were evaluated in a doxycycline-induced zebrafish HCC model and xenograft mouse model.Results: NMOFs-RGD had low biotoxicity, good biocompatibility and excellent imaging capability. In HCC-bearing zebrafish, HCPT@NMOFs-RGD were specifically enriched in the tumor by binding specifically to integrin αvβ3 and led to a reduction in tumor volume. Moreover, the xenografts in mice were eliminated remarkably following HCPT@NMOFs-RGD treatment with laser irradiation, while little morphological change was found in other main organs.Conclusion: The nanocomposites HCPT@NMOFs-RGD accomplish tumor targeting and play synergistic chemo- and photodynamic therapeutic effects on HCC, offering a novel imaging-guided drug delivery and theranostic platform.Keywords: zirconium porphyrin metal-organic frameworks, 10-hydroxycamptothecin, hepatocellular carcinoma, chemotherapy, photodynamic therapy
