scholarly journals A combined miR-34a and arsenic trioxide nanodrug delivery system for synergistic inhibition of HCC progression after microwave ablation

Author(s):  
Jian Hu ◽  
Wenceng Pei ◽  
Zhenyou Jiang ◽  
Zihuang Li

Abstract Background Microwave ablation (MWA) has become an alternative treatment for unresectable surgery for hepatocellular carcinoma (HCC), but it still faces the risk of recurrence and metastasis after treatment. Recent studies have found that miR-34a presents decreased gene expression in residual tumours after ablation therapy and can increase the therapeutic effect of arsenic trioxide on HCC, which brings new opportunities for its treatment. Methods A pH-sensitive charge inversion material was used to construct a nanotargeted delivery system that presents the synergistic effect of miR-34a and As2O3. We established in vitro and in vivo models of microwave ablation of HCC and performed in-depth research on dual drug systems to inhibit the rapid progression of HCC after microwave ablation in cell pyroptosis. Results The antitumour effect was enhanced with double-drug nanoparticles relative to a single formulation, and the therapeutic efficacy of the nanoparticles was more significant in a weakly acidic environment. Dual-drug nanoparticles could increase the N-terminal portion of GSDME, decrease the expression of Cyt-c and c-met. Conclusions Dual-drug nanoparticles may improve the therapeutic efficacy of HCC with insufficient ablation through Cyt-c and GSDME-N and decrease the expression levels of c-met. It is expected to provide new treatment methods for residual liver cancer after microwave ablation, prolong the survival of patients and improve quality of life.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jian Hu ◽  
Wenceng Pei ◽  
Zhenyou Jiang ◽  
Zihuang Li

Abstract Background Microwave ablation (MWA) has become an alternative treatment for unresectable hepatocellular carcinoma (HCC), but it does not eliminate the risk of recurrence and metastasis after treatment. Recent studies have demonstrated that miR-34a presents decreased gene expression in residual tumours after ablation therapy and can increase the therapeutic effect of arsenic trioxide against HCC, which brings new opportunities for HCC treatment. Methods A pH-sensitive charge inversion material was used to construct a nanotargeted delivery system based on the synergistic effects of miR-34a and As2O3. We established in vitro and in vivo models of HCC microwave ablation and performed in-depth research on the dual-drug system to inhibit the rapid progression and induce pyroptosis in HCC cells after microwave ablation. Results The antitumour effects were enhanced with the dual-drug nanoparticles relative to the single-drug formulations, and the therapeutic efficacy of the nanoparticles was more significant in a weakly acidic environment. The dual-drug nanoparticles increased the N-terminal portion of GSDME and decreased the expression of Cyt-c and c-met. Conclusions Dual-drug nanoparticles may improve the therapeutic efficacy of HCC treatment after insufficient ablation through Cyt-c and GSDME-N and decrease the expression levels of c-met. These nanoparticles are expected to provide new treatment methods for residual HCC after MWA, prolong the survival of patients and improve their quality of life.


2019 ◽  
Vol 7 (9) ◽  
pp. 3662-3674 ◽  
Author(s):  
Yiming Liu ◽  
Ke Li ◽  
Youshen Wu ◽  
Jingwen Ma ◽  
Peng Tang ◽  
...  

A novel carrier-free dual-drug delivery system (HA-Gn@DPGn NPs) realizes ultralow dose DOX administration while ensuring high tumor comprehensive synergistic therapeutic efficacy.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 848
Author(s):  
Luisa Stella Dolci ◽  
Rosaria Carmela Perone ◽  
Roberto Di Gesù ◽  
Mallesh Kurakula ◽  
Chiara Gualandi ◽  
...  

Vascular and traumatic injuries of the central nervous system are recognized as global health priorities. A polypharmacology approach that is able to simultaneously target several injury factors by the combination of agents having synergistic effects appears to be promising. Herein, we designed a polymeric delivery system loaded with two drugs, ibuprofen (Ibu) and thyroid hormone triiodothyronine (T3) to in vitro release the suitable amount of the anti-inflammation and the remyelination drug. As a production method, electrospinning technology was used. First, Ibu-loaded micro (diameter circa 0.95–1.20 µm) and nano (diameter circa 0.70 µm) fibers were produced using poly(l-lactide) PLLA and PLGA with different lactide/glycolide ratios (50:50, 75:25, and 85:15) to select the most suitable polymer and fiber diameter. Based on the in vitro release results and in-house knowledge, PLLA nanofibers (mean diameter = 580 ± 120 nm) loaded with both Ibu and T3 were then successfully produced by a co-axial electrospinning technique. The in vitro release studies demonstrated that the final Ibu/T3 PLLA system extended the release of both drugs for 14 days, providing the target sustained release. Finally, studies in cell cultures (RAW macrophages and neural stem cell-derived oligodendrocyte precursor cells—OPCs) demonstrated the anti-inflammatory and promyelinating efficacy of the dual drug-loaded delivery platform.


1993 ◽  
Vol 67 (8) ◽  
pp. 580-585 ◽  
Author(s):  
Helmut Kreppel ◽  
Uwe Paepcke ◽  
Horst Thiermann ◽  
Ladislaus Szinicz ◽  
Franz X. Reichl ◽  
...  

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