Fluorescent Imaging-Guided Chemo- and Photodynamic Therapy of Hepatocellular Carcinoma with HCPT@NMOFs-RGD Nanocomposites

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 α v β 3 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.

Research development of porphyrin-based metal–organic frameworks: targeting modalities and cancer therapeutic applications

“…213 Shang and coworkers loaded HCPT into the pores of nanoscale zirconium porphyrin metal–organic frameworks (NMOFs) with a stable structure and excellent biocompatibility, and coated with RGD polypeptide (HCPT@NMOFs-RGD) to obtain targeting ability. 214 HCPT@NMOFs-RGD greatly reduces the toxic and side effects of chemotherapy, and precisely targets the PDT/chemotherapy synergistic treatment to the tumor parts of HCC. For cancer cells, the highly expressed GSH in TME cleaved disulfide bonds (−S−S−).…”

Metal-organic frameworks for hepatocellular carcinoma therapy and mechanism

“…This dual-mode imaging strategy provides extremely valuable information to elucidate biological processes related to CTR1. Shang et al (2022) prepared a zirconium porphyrin metal organic framework (NMOFs) and then loaded 10hydroxycamptothecin (HCPT) into the pores of the NMOFs and wrapped it with arginine glycine aspartic acid (RGD) peptide to obtain a new nanocomposite HCPT@NMOFs-RGD (Figure 8). In a mouse tumor model with xenograft, the antitumor activity of HCPT@NMOFs-RGD was evaluated.…”

Recent Advances in Tetrakis (4‐Carboxyphenyl) Porphyrin‐Based Nanocomposites for Tumor Therapy

“…The integrin α v β 3 on the surface of hepatocellular carcinoma cells has been used as a target for hepatocellular carcinoma (HCC). Li's group [ 36 ] designed and prepared a novel HCPT@ nanometal–organic frameworks (NMOFs)‐RGD nanocomposite that could target HCC. 10‐hydroxycamptothecin (HCPT) is a topoisomerase I inhibitor that inhibits cell proliferation and has broad antitumor activity against breast, colon, lung, and ovarian cancer in clinical practice.…”

“…CAT-TCPP/FCS --PDT [30] PEG-HNRs -FL - [31] CHC-PZM@HA Zr 6 PDT [32] HCPT@MOF-S-S-HA Zr 6 FL/MR/Thermal imaging Chemotherapy/PDT/PTT [33] Zr-MOF-aptamer-TAMRA Zr 6 FL PDT [34] CM-MMNPs Zr 6 -PDT [35] HCPT@NMOFs-RGD nanocomposite Zr 6 -Chemotherapy/PDT [36] 89…”

“…TCPP-based MOFs could load chemotherapy drugs and prevent their leakage, which greatly reduces the damage to normal tissues. [36,56] In addition, some biological enzymes or immune adjuvants cannot play a role in the complex physiological environment and are easy to be removed. These substances loaded by MOFs, on the one hand, prolong the blood circulation time, in contrast, through active or passive targeted accumulation in the tumor site, better play the catalytic or immune activation properties in vivo.…”