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

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

Synthesis of zeolitic imidazolate framework-8 and gold nanoparticles in a sustained out-of-equilibrium state

The design and synthesis of crystalline materials are challenging due to the proper control over the size and polydispersity of the samples, which determine their physical and chemical properties and thus applicability. Metal − organic frameworks (MOFs) are promising materials in many applications due to their unique structure. MOFs have been predominantly synthesized by bulk methods, where the concentration of the reagents gradually decreased, which affected the further nucleation and crystal growth. Here we show an out-of-equilibrium method for the generation of zeolitic imidazolate framework-8 (ZIF-8) crystals, where the non-equilibrium crystal growth is maintained by a continuous two-side feed of the reagents in a hydrogel matrix. The size and the polydispersity of the crystals are controlled by the fixed and antagonistic constant mass fluxes of the reagents and by the reaction time. We also present that our approach can be extended to synthesize gold nanoparticles in a redox process.

Remedy for Collapse of ZIF Derived Carbon: Micro-Pore Filled Synthesis to Improve ORR Catalytic Property

Zeolitic imidazolate framework (ZIF) derived carbons deliver outstanding performance as oxygen reduction reaction (ORR) catalysts. However, their electrocatalytic activities are limited due to unavoidable collapse of ZIFs upon pyrolysis, which results in degradation of porosity, sintering of metals and loss of active sites. In this work, a micro-pore filling strategy was employed to strength the architecture of ZIF by using size matched cyanamide molecules as fillers. The cyanamide with high nitrogen content shows a triple effect in stabilizing the carbonaceous skeleton, preserving of metal containing active sites and improving the conductivity of matrix. Therefore, the as-prepared Fe, Co co-doped ZIF derived carbon (FeCo@NC-N) delivers a significantly improved electrochemical activity for ORR than its unfilled counterpart, with half-wave potential upshifted by 30 mV (0.84 V vs. RHE). Besides, a promoted power density of home-assembled zinc-air battery is obtained when FeCo@NC-N is applied as cathode catalyst. This work demonstrates a reliable approach to mitigate framework collapse of metal organic framework (MOF), thus may open a new way for fabrication of MOF based catalysts with increased loading of pores and active sites.