Fluorescent Imaging-Guided Chemo- and Photodynamic Therapy of Hepatocellular Carcinoma with HCPT@NMOFs-RGD Nanocomposites
Yue Shang, Hui Zhang, Yajia Cheng, Peipei Cao, Jianlin Cui, Xuebo Yin, Saijun Fan, Yuhao Li
Abstract
Background: 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, [email protected] The tissue distribution and chemo- and photodynamic therapeutic effects of [email protected] 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, [email protected] were specifically enriched in the tumor by binding specifically to integrin α v β 3 and led to a reduction in tumor volume. Moreover, the xenografts in mice were eliminated remarkably following [email protected] treatment with laser irradiation, while little morphological change was found in other main organs. Conclusion: The nanocomposites [email protected] 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