PUBLICATION
Fluorescent Imaging-Guided Chemo- and Photodynamic Therapy of Hepatocellular Carcinoma with HCPT@NMOFs-RGD Nanocomposites
- Authors
- Shang, Y., Zhang, H., Cheng, Y., Cao, P., Cui, J., Yin, X., Fan, S., Li, Y.
- ID
- ZDB-PUB-220405-8
- Date
- 2022
- Source
- International Journal of Nanomedicine 17: 1381-1395 (Journal)
- Registered Authors
- Cui, Jianlin, Li, Yuhao, Zhang, Hui
- Keywords
- 10-hydroxycamptothecin, chemotherapy, hepatocellular carcinoma, photodynamic therapy, zirconium porphyrin metal-organic frameworks
- MeSH Terms
-
- Animals
- Camptothecin/analogs & derivatives
- Carcinoma, Hepatocellular*/diagnostic imaging
- Carcinoma, Hepatocellular*/drug therapy
- Humans
- Liver Neoplasms*/diagnostic imaging
- Liver Neoplasms*/drug therapy
- Mice
- Nanocomposites*
- Oligopeptides
- Photochemotherapy*
- Zebrafish
- PubMed
- 35369034 Full text @ Int. J. Nanomedicine
Citation
Shang, Y., Zhang, H., Cheng, Y., Cao, P., Cui, J., Yin, X., Fan, S., Li, Y. (2022) Fluorescent Imaging-Guided Chemo- and Photodynamic Therapy of Hepatocellular Carcinoma with HCPT@NMOFs-RGD Nanocomposites. International Journal of Nanomedicine. 17:1381-1395.
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, 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping