Local application of doxorubicin- loaded Iron oxid nanoparticles and the vascular disrupting agent via the hepatic artery: chemoembolization–photothermal ablation treatment of hepatocellular carcinoma in rats

Abstract Objectives This study investigates the effectiveness of local application of doxorubicin(Dox)-loaded, polydopamine (PDA)- coated single crystal hematite (α- Fe2O3) nanocubes (Fe2O3-PDA-Dox) and combretastatin A-4 phosphate disodium(CA4P)in treating hepatocellular carcinoma (HCC) in rats. Methods The magnetic characteristics and photothermal effects of the nanoparticles were determined in vitro. Tumor-bearing Sprague–Dawley rats were divided into 3 groups of 8 according to treatment: controls, transarterial chemoembolization–photothermal ablation (pTACE) (Lipidol+Fe2O3-PDA-Dox + NIR), and CA4P + pTACE (CA4P+ Lipidol+Fe2O3-PDA-Dox + NIR). Drugs were administered through the hepatic artery, and the tumors exposed to 808-nm near-infrared radiation. The Fe content of tumors was assessed using neutron activation analysis. Treatment effectiveness was assessed using heating curves, magnetic resonance imaging, pathology results, and immunohistochemical analysis. Results The mean tumor Fe content was greater in rats treated with CA4P + pTACE (1 h, 23.72 ± 12.45 μg/g; 24 h, 14.61 ± 8.23 μg/g) than in those treated with pTACE alone (1 h, 5.66 ± 4.29 μg/g; 24 h, 2.76 ± 1.33 μg/g). The tumor T2 imaging signal was lower in rats treated with CA4P + pTACE. Following laser irradiation, the tumor temperature increased, with higher temperatures reached in the CA4P + pTACE group (62 °C vs 55 °C). Tumor cells exhibited necrosis, apoptosis, and proliferation inhibition, with greater effects in the CA4P + pTACE group. Transient liver and kidney toxicity were observed on day 3, with more severe effects after CA4P + pTACE. Conclusions Fe2O3-PDA-Dox nanoparticles are effective for TACE–PTA. Pretreatment with CA4P increases nanoparticle uptake by tumors, increasing the treatment effectiveness without increasing hepatorenal toxicity.

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Synergistic Antitumor Effect of 5-Fluorouracil Combined with Constituents from Pleurospermum lindleyanum in Hepatocellular carcinoma SMMC-7721 Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200824094624 ◽

2020 ◽

Vol 20 ◽

Author(s):

Xiao-Feng Zhu ◽

Xiao-Jin Li ◽

Zhong-Lian Cao ◽

Xiu-Jie Liu ◽

Ping Yang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Treatment Effectiveness ◽

Synergistic Effects ◽

Folk Medicine ◽

Inhibitory Effect ◽

Caspase 9 ◽

Whole Plant ◽

Anti Cancer ◽

Induced Apoptosis

Background: A Chinese folk medicine plant Pleurospermum lindleyanum possesses pharmacological activities of heat-clearing, detoxifying and preventing from hepatopathy, coronary heart disease, hypertension, and high altitude sickness. We isolated and characterized its constituents to investigate its synergistic effects against human hepatoma SMMC-7721 cells. Objective: The aim of this study was to explore the synergistic anti-cancer activities of isolates from P. lindleyanum with 5-FU on hepatoma SMMC-7721 cells in vitro and their primary mechanisms. Methods: Sequential chromatographic techniques were conducted for the isolation studies. The isolates structures were established by spectroscopic analysis as well as X-ray crystallographic diffraction. Growth inhibition was detected by MTT assay. The isobologram method was used to assess the effect of drug combinations. Flow cytometry and western blot were used to examine apoptosis and protein expression. Results: A new coumarin (16), along with sixteen known compounds, were isolated from the whole plant of P. lindleyanum and their structures were elucidated by spectroscopic methods. Four coumarins (2, 3, 5, and 16), two flavonoids (8 and 9) and three phytosterols and triterpenes (12-14) were found to synergistically enhance the inhibitory effect of 5-FU against SMMC-7721 cells. Among them, compounds 3 and 16 exhibited the best synergistic effects with IC50 of 5-FU reduced by 16-fold and 22-fold possessing the minimum Combination Index (CI) 0.34 and 0.27. The mechanism of action of combinations might be through synergistic arresting for the cell cycle at G1 phases and the induction of apoptosis. Moreover, western blotting and molecular docking revealed that compounds 3 or 5 might promote 5-FU-induced apoptosis by regulating the expression of Caspase 9 and PARP. Conclusion: Constituents from P. lindleyanum may improve the treatment effectiveness of 5-FU against hepatocellular carcinoma cells.

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Impact of Iron on the Fe–Co–Ni Ternary Nanocomposites Structural and Magnetic Features Obtained via Chemical Precipitation Followed by Reduction Process for Various Magnetically Coupled Devices Applications

Nanomaterials ◽

10.3390/nano11020341 ◽

2021 ◽

Vol 11 (2) ◽

pp. 341

Author(s):

Tien Hiep Nguyen ◽

Gopalu Karunakaran ◽

Yu.V. Konyukhov ◽

Nguyen Van Minh ◽

D.Yu. Karpenkov ◽

...

Keyword(s):

Particle Size ◽

Magnetic Properties ◽

Reduction Process ◽

Chemical Precipitation ◽

Precipitation Method ◽

Magnetic Characteristics ◽

Reduction Temperature ◽

Fe Content ◽

Magnetic Features ◽

Co Precipitation

This paper presents the synthesis of Fe–Co–Ni nanocomposites by chemical precipitation, followed by a reduction process. It was found that the influence of the chemical composition and reduction temperature greatly alters the phase formation, its structures, particle size distribution, and magnetic properties of Fe–Co–Ni nanocomposites. The initial hydroxides of Fe–Co–Ni combinations were prepared by the co-precipitation method from nitrate precursors and precipitated using alkali. The reduction process was carried out by hydrogen in the temperature range of 300–500 °C under isothermal conditions. The nanocomposites had metallic and intermetallic phases with different lattice parameter values due to the increase in Fe content. In this paper, we showed that the values of the magnetic parameters of nanocomposites can be controlled in the ranges of MS = 7.6–192.5 Am2/kg, Mr = 0.4–39.7 Am2/kg, Mr/Ms = 0.02–0.32, and HcM = 4.72–60.68 kA/m by regulating the composition and reduction temperature of the Fe–Co–Ni composites. Due to the reduction process, drastic variations in the magnetic features result from the intermetallic and metallic face formation. The variation in magnetic characteristics is guided by the reduction degree, particle size growth, and crystallinity enhancement. Moreover, the reduction of the surface spins fraction of the nanocomposites under their growth induced an increase in the saturation magnetization. This is the first report where the influence of Fe content on the Fe–Co–Ni ternary system phase content and magnetic properties was evaluated. The Fe–Co–Ni ternary nanocomposites obtained by co-precipitation, followed by the hydrogen reduction led to the formation of better magnetic materials for various magnetically coupled device applications.

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Molecularly targeted photothermal ablation improves tumor specificity and immune modulation in a rat model of hepatocellular carcinoma

Communications Biology ◽

10.1038/s42003-020-01522-y ◽

2020 ◽

Vol 3 (1) ◽

Author(s):

Nina M. Muñoz ◽

Crystal Dupuis ◽

Malea Williams ◽

Katherine Dixon ◽

Amanda McWatters ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Indocyanine Green ◽

Tumor Immunity ◽

Rat Model ◽

Thermal Ablation ◽

Immune Modulation ◽

Photothermal Ablation ◽

Profiling Techniques ◽

Tumor Immunogenicity ◽

Tumor Specificity

AbstractThermal ablation is a standard therapy for patients with hepatocellular carcinoma (HCC). Contemporary ablation devices are imperfect, as they lack tumor specificity. An ideal ablation modality would generate thermal energy only within tumoral tissue. Furthermore, as hyperthermia is known to influence tumor immunity, such a tumor-specific ablation modality may have the ability to favorably modulate the tumor immune landscape. Here we show a clinically relevant thermal ablation modality that generates tumor-specific hyperthermia, termed molecularly targeted photothermal ablation (MTPA), that is based upon the excellent localization of indocyanine green to HCC. In a syngeneic rat model, we demonstrate the tumor-specific hyperthermia generated by MTPA. We also show through spatial and transcriptomic profiling techniques that MTPA favorably modulates the intratumoral myeloid population towards tumor immunogenicity and diminishes the systemic release of oncogenic cytokines relative to conventional ablation modalities.

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Tumor metabolism and associated serum metabolites define prognostic subtypes of Asian hepatocellular carcinoma

Scientific Reports ◽

10.1038/s41598-021-91560-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yotsawat Pomyen ◽

Anuradha Budhu ◽

Jittiporn Chaisaingmongkol ◽

Marshonna Forgues ◽

Hien Dang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Fatty Acid ◽

Fatty Acid Metabolism ◽

Acid Metabolism ◽

Treatment Effectiveness ◽

Data Types ◽

Serum Metabolites ◽

Non Invasive ◽

Metabolic Genes ◽

Tissue Metabolites

AbstractTreatment effectiveness in hepatocellular carcinoma (HCC) depends on early detection and precision-medicine-based patient stratification for targeted therapies. However, the lack of robust biomarkers, particularly a non-invasive diagnostic tool, precludes significant improvement of clinical outcomes for HCC patients. Serum metabolites are one of the best non-invasive means for determining patient prognosis, as they are stable end-products of biochemical processes in human body. In this study, we aimed to identify prognostic serum metabolites in HCC. To determine serum metabolites that were relevant and representative of the tissue status, we performed a two-step correlation analysis to first determine associations between metabolic genes and tissue metabolites, and second, between tissue metabolites and serum metabolites among 49 HCC patients, which were then validated in 408 additional Asian HCC patients with mixed etiologies. We found that certain metabolic genes, tissue metabolites and serum metabolites can independently stratify HCC patients into prognostic subgroups, which are consistent across these different data types and our previous findings. The metabolic subtypes are associated with β-oxidation process in fatty acid metabolism, where patients with worse survival outcome have dysregulated fatty acid metabolism. These serum metabolites may be used as non-invasive biomarkers to define prognostic tumor molecular subtypes for HCC.

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A novel antibody targeting CD24 and hepatocellular carcinoma in vivo by near-infrared fluorescence imaging

Immunobiology ◽

10.1016/j.imbio.2015.07.010 ◽

2015 ◽

Vol 220 (12) ◽

pp. 1328-1336 ◽

Cited By ~ 15

Author(s):

Hua He ◽

Xiaojie Tu ◽

Juan Zhang ◽

Desmond Omane Acheampong ◽

Li Ding ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Fluorescence Imaging ◽

Near Infrared ◽

Near Infrared Fluorescence ◽

Antibody Targeting ◽

Near Infrared Fluorescence Imaging

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Changes in Hepatic Hemodynamics due to Primary Liver Tumours

HPB Surgery ◽

10.1155/1996/62057 ◽

1996 ◽

Vol 9 (4) ◽

pp. 245-248 ◽

Cited By ~ 9

Author(s):

F. Jakab ◽

Z. Ráth ◽

F. Schmal ◽

P. Nagy ◽

J. Faller

Keyword(s):

Hepatocellular Carcinoma ◽

Blood Flow ◽

Hepatic Artery ◽

Hepatic Blood Flow ◽

Primary Hepatocellular Carcinoma ◽

Portal Venous Flow ◽

Venous Flow ◽

Control Value ◽

Early Results ◽

Total Hepatic Blood Flow

Data regarding the afferent circulation of the liver in patients with primary hepatocellular carcinoma are controversial, we have carried out measurement of hepatic arterial and portal venous flow intraoperatively by transit time ultrasonic volume flowmetry. In patients with primary hepatocellular carcinoma the hepatic artery flow increased to 0.55±0.211 compared with the control value of 0.37±0.102 1/min. (p<0.01). The portal venous flow decreased from 0.61±0.212 l/min, to 0.47±l/min. p<0.01). Due to the opposite changes in the afferent circulation the total hepatic blood flow did not change significantly, compared with controls.The ratio of hepatic arterial flow to portal vein flow increased to 1.239±0.246 in patients with hepatocellular carcinoma, which is double of the control value (0.66±0.259 l/min). After resection this ratio did not change.The resection did not alter hepatic artery or portal venous flow significantly, although the total hepatic blood flow decreased significantly (p<0.01).On the basis of our early results it is possible that the ratio of the two circulations may be to deel measured with doppler ultrasound and provide diagnostic information.

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