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

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.

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

10.21203/rs.3.rs-609280/v1 ◽

2021 ◽

Author(s):

Jian Hu ◽

Wenceng Pei ◽

Zhenyou Jiang ◽

Zihuang Li

Keyword(s):

Arsenic Trioxide ◽

Delivery System ◽

Therapeutic Efficacy ◽

Microwave Ablation ◽

Rapid Progression ◽

In Vivo Models ◽

Treatment Methods ◽

Drug Nanoparticles ◽

Cyt C ◽

Dual Drug

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.

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Design and In Vitro Study of a Dual Drug-Loaded Delivery System Produced by Electrospinning for the Treatment of Acute Injuries of the Central Nervous System

Pharmaceutics ◽

10.3390/pharmaceutics13060848 ◽

2021 ◽

Vol 13 (6) ◽

pp. 848

Author(s):

Luisa Stella Dolci ◽

Rosaria Carmela Perone ◽

Roberto Di Gesù ◽

Mallesh Kurakula ◽

Chiara Gualandi ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Delivery System ◽

Synergistic Effects ◽

In Vitro Release ◽

Health Priorities ◽

The Central Nervous System ◽

Vitro Release ◽

Dual Drug

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.

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PVA reinforced gossypolone and doxorubicin π–π stacking nanoparticles towards tumor targeting and ultralow dose synergistic chemotherapy

Biomaterials Science ◽

10.1039/c9bm00674e ◽

2019 ◽

Vol 7 (9) ◽

pp. 3662-3674 ◽

Cited By ~ 3

Author(s):

Yiming Liu ◽

Ke Li ◽

Youshen Wu ◽

Jingwen Ma ◽

Peng Tang ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Therapeutic Efficacy ◽

Tumor Targeting ◽

Ultralow Dose ◽

Π Stacking ◽

Carrier Free ◽

Dual Drug

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.

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pH-controlled nucleolin targeted release of dual drug from chitosan-gold based aptamer functionalized nano drug delivery system for improved glioblastoma treatment

Carbohydrate Polymers ◽

10.1016/j.carbpol.2021.117907 ◽

2021 ◽

Vol 262 ◽

pp. 117907

Author(s):

Anbazhagan Sathiyaseelan ◽

Kandasamy Saravanakumar ◽

Arokia Vijaya Anand Mariadoss ◽

Myeong-Hyeon Wang

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Delivery System ◽

Nano Drug Delivery ◽

Targeted Release ◽

Dual Drug ◽

Ph Controlled

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A promising dual-drug targeted delivery system in cancer therapy: nanocomplexes of folate–apoferritin-conjugated cationic solid lipid nanoparticles

Pharmaceutical Development and Technology ◽

10.1080/10837450.2021.1920037 ◽

2021 ◽

pp. 1-9

Author(s):

Abbas Amer Ridha ◽

Soheila Kashanian ◽

Ronak Rafipour ◽

Abbas Hemati Azandaryani ◽

Hossein Zhaleh ◽

...

Keyword(s):

Cancer Therapy ◽

Delivery System ◽

Targeted Delivery ◽

Solid Lipid Nanoparticles ◽

Lipid Nanoparticles ◽

Solid Lipid ◽

Targeted Delivery System ◽

Dual Drug

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Synergistic Effects of N-Acetylcysteine and Mesenchymal Stem Cell in a Lipopolysaccharide-Induced Interstitial Cystitis Rat Model

Cells ◽

10.3390/cells9010086 ◽

2019 ◽

Vol 9 (1) ◽

pp. 86 ◽

Cited By ~ 1

Author(s):

Jung Hyun Shin ◽

Chae-Min Ryu ◽

Hyein Ju ◽

Hwan Yeul Yu ◽

Sujin Song ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Interstitial Cystitis ◽

Rat Model ◽

Therapeutic Efficacy ◽

Synergistic Effects ◽

Embryonic Stem ◽

Protamine Sulfate ◽

Sprague Dawley ◽

Multipotent Mesenchymal Stem Cells

The purpose of this study was to reduce the amount of stem cells used in treating preclinical interstitial cystitis (IC model) by investigating the synergistic effects of multipotent mesenchymal stem cells (M-MSCs; human embryonic stem cell-derived) and N-acetylcysteine (NAC). Eight-week-old female Sprague-Dawley rats were divided into seven groups, i.e., sham (n = 10), lipopolysaccharide/protamine sulfate (LPS/PS; n = 10), LPS/PS + NAC (n = 10), LPS/PS with 25K MSC (n = 10), LPS/PS with 50K MSC (n = 10) LPS/PS + 25K MSC + NAC (n = 10), and LPS/PS + 50K MSC + NAC (n = 10). To induce the IC rat model, protamine sulfate (10 mg, 45 min) and LPS (750 μg, 30 min) were instilled once a week for five consecutive weeks via a transurethral PE-50 catheter. Phosphate-buffered saline (PBS) was used in the sham group. One week after the final instillation, M-MSCs with two suboptimal dosages (i.e., 2.5 or 5.0 × 104 cells) were directly transplanted into the outer-layer of the bladder. Simultaneously, 200 mg/kg of NAC or PBS was intraperitoneally injected daily for five days. The therapeutic outcome was evaluated one week after M-MSC or PBS injection by awake cystometry and histological analysis. Functionally, LPS/PS insult led to irregular micturition, decreased intercontraction intervals, and decreased micturition volume. Both monotherapy and combination therapy significantly increased contraction intervals, increased urination volume, and reduced the residual volume, thereby improving the urination parameters compared to those of the LPS group. In particular, a combination of NAC dramatically reduced the amount of M-MSCs used for significant restoration in histological damage, including inflammation and apoptosis. Both M-MSCs and NAC-based therapy had a beneficial effect on improving voiding dysfunction, regenerating denudated urothelium, and relieving tissue inflammation in the LPS-induced IC/BPS rat model. The combination of M-MSC and NAC was superior to MSC or NAC monotherapy, with therapeutic efficacy that was comparable to that of previously optimized cell dosage (1000K) without compromised therapeutic efficacy.

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