Augmented EPR effect post IRFA to enhance the therapeutic efficacy of arsenic loaded ZIF-8 nanoparticles on residual HCC progression

Abstract

Background Insufficient radiofrequency ablation (IRFA) can promote the local recurrence and distal metastasis of residual hepatocellular carcinoma (HCC), which makes clinical treatment extremely challenging. In this study, the malignant transition of residual tumors after IRFA was explored. Then, arsenic-loaded zeolitic imidazolate framework-8 nanoparticles (As@ZIF-8 NPs) were constructed, and their therapeutic effect on residual tumors was studied. Results Our data showed that IRFA can dramatically promote the proliferation, induce the metastasis, activate the epithelial–mesenchymal transition (EMT) and accelerate the angiogenesis of residual tumors. Interestingly, we found, for the first time, that extensive angiogenesis after IRFA can augment the enhanced permeability and retention (EPR) effect and enhance the enrichment of ZIF-8 nanocarriers in residual tumors. Encouraged by this unique finding, we successfully prepared As@ZIF-8 NPs with good biocompatibility and confirmed that they were more effective than free arsenic trioxide (ATO) in sublethal heat-induced cell proliferation suppression, apoptosis induction, cell migration and invasion inhibition, and EMT reversal in vitro. Furthermore, compared with free ATO, As@ZIF-8 NPs exhibited remarkably increased therapeutic effects by repressing residual tumor growth and metastasis in vivo. Conclusions This work provides a new paradigm for the treatment of residual HCC after IRFA. Graphical Abstract

Correction to: Augmented EPR effect post IRFA to enhance the therapeutic efficacy of arsenic loaded ZIF-8 nanoparticles on residual HCC progression

“…Following publication of the original article [ 1 ], the authors reported that Fig. 4 C was incorrect.…”

Progression of hepatocellular carcinoma after radiofrequency ablation: Current status of research

“…Chen et al. ( 105 )also found that extensive angiogenesis after RFA could augment the enhanced permeability and retention effect and increase the enrichment of ATO-loaded ZIF-8 nanoparticles, which markedly inhibited residual tumor progression.…”

Metal-organic frameworks for hepatocellular carcinoma therapy and mechanism

“…In another study, Chen et al (2022 ) used ZIF-8 as the backbone and loaded with arsenic trioxide (ATO) to develop the NPs As@ZIF-8. These NPs were then encapsulated in COOH-PEG-COOH to obtain As@ZIF-8/PEG NPs, which improved their pharmacokinetic properties ( Figure 5 ).…”