A novel platform for drug testing: Biomimetic three-dimensional hyaluronic acid-based scaffold seeded with human hepatocarcinoma cells

Turtoi, Mihaela; Anghelache, Maria; Bucatariu, Sanda-Maria; Deleanu, Mariana; Voicu, Geanina; Safciuc, Florentina; Manduteanu, Ileana; Fundueanu, Gheorghe; Simionescu, Maya; Calin, Manuela

doi:10.1016/j.ijbiomac.2021.06.174

Cited by 26 publications

(14 citation statements)

References 49 publications

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“…The cytotoxicity of various concentrations of MNP-Dex/PCA, as well as of plain MNP-Dex and PCA, was assessed on M1 macrophages after 24 and 48 h and EC after 48 h of incubation using the ToxiLightTM BioAssay Kit (Lonza Bioscience, Basel, Switzerland) [25]. The release of adenylate kinase in the cell medium indicates a loss of cell integrity, which can be quantified by bioluminescent detection.…”

Section: Bioluminescent Assaymentioning

confidence: 99%

Development of Dextran-Coated Magnetic Nanoparticles Loaded with Protocatechuic Acid for Vascular Inflammation Therapy

Anghelache

Turtoi

Petrovici³

et al. 2021

Pharmaceutics

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Vascular inflammation plays a crucial role in the progression of various pathologies, including atherosclerosis (AS), and thus it has become an attractive therapeutic target. The protocatechuic acid (PCA), one of the main metabolites of complex polyphenols, is endowed with anti-inflammatory activity, but its formulation into nanocarriers may increase its bioavailability. In this study, we developed and characterized dextran shell‒iron oxide core nanoparticles loaded with PCA (MNP-Dex/PCA) and assessed their cytotoxicity and anti-inflammatory potential on cells acting as key players in the onset and progression of AS, namely, endothelial cells (EC) and monocytes/macrophages. The results showed that MNP-Dex/PCA exert an anti-inflammatory activity at non-cytotoxic and therapeutically relevant concentrations of PCA (350 μM) as supported by the reduced levels of inflammatory molecules such as MCP-1, IL-1β, TNF-α, IL-6, and CCR2 in activated EC and M1-type macrophages and functional monocyte adhesion assay. The anti-inflammatory effect of MNP-Dex/PCA was associated with the reduction in the levels of ERK1/2 and p38-α mitogen-activated protein kinases (MAPKs) and NF-kB transcription factor. Our data support the further development of dextran shell-magnetic core nanoparticles as theranostic nanoparticles for guidance, imaging, and therapy of vascular inflammation using PCA or other anti-inflammatory compounds.

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Section: Bioluminescent Assaymentioning

confidence: 99%

Development of Dextran-Coated Magnetic Nanoparticles Loaded with Protocatechuic Acid for Vascular Inflammation Therapy

Anghelache

Turtoi

Petrovici³

et al. 2021

Pharmaceutics

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“…Hepatocellular carcinoma is a liver cancer most often associated with various chronic liver diseases and cirrhosis, which remains one of the most prevalent cancers all over the world [ 25 ]. The use of platinum-based drugs, like cisplatin, carboplatin, or oxaliplatin in the treatment of various cancers, is well documented, however, despite their great antitumor activity, severe side effects associated with drug resistance limit their effectiveness [ 3 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…Cell cycle arrest is directly involved in reducing cell growth/division and together with the cellular response to DNA damage may be associated with cytoskeletal remodeling and decreased polymerization of the microtubules’ components, α- and β-Tubulin [ 51 ]. We have previously shown the involvement of cisplatin in DNA fragmentation, the cytoskeleton remodeling, and β-Tubulin synthesis reduction in human hepatocellular carcinoma cells [ 25 ]. Herein, we showed that TetraV V reduced β-Tubulin synthesis after 24 h of treatment probably due to the association between ROS generation, MtMP reduction, DNA fragmentation, and cell cycle arrest in the S and G2/M-phase.…”

Section: Discussionmentioning

confidence: 99%

“…The Live/Dead assay kit which consists of the Calcein-AM/propidium iodide (PI) staining method was also used for studying the cytotoxicity of TetraV V and cisplatin at the corresponding IC 50 concentrations. The staining protocol and the image acquisition were performed as we previously described [ 25 ]. The samples investigation was done with the 20× objective of the Inverted Microscope Olympus IX81 equipped with TRITC (λ ex /λ em = 555 nm/580 nm) and FITC (λ ex /λ em = 494 nm/518 nm) filters (Olympus Corporation, Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…To study the ability of TetraV V and cisplatin to induce DNA fragmentation into the treated cells, the acridine orange (AO) staining was used [ 25 ]. After drug treatment, HepG2 cells were washed three times with PBS, fixed with 4% PFA, permeabilized with 0.2% Triton X-100, and stained with AO (6 µg/mL in 0.2 M Na 2 HPO 4 , pH = 2.6/0.1 M citric acid).…”

Section: Methodsmentioning

confidence: 99%

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Antitumor Properties of a New Macrocyclic Tetranuclear Oxidovanadium(V) Complex with 3-Methoxysalicylidenvaline Ligand

et al. 2022

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A wide variety of metal-based compounds have been obtained and studied for their antitumor activity since the intensely used cytostatic drugs (e.g., cisplatin) failed to accomplish their expected pharmacological properties. Thus, we aimed to develop a new vanadium-based drug and assess its antitumor properties using the human hepatocarcinoma (HepG2) cell line. The compound was synthesized from vanadyl sulfate, DL-valine, and o-vanillin and was spectrally and structurally characterized (UV-Vis, IR, CD, and single-crystal/powder-XRD). Compound stability in biological media, cell uptake, and the interaction with albumin were assessed. The mechanisms of its antitumor activity were determined compared to cisplatin by performing cytotoxicity, oxidative and mitochondrial status, DNA fragmentation, β-Tubulin synthesis investigation, and cell cycle studies. Herein, we developed a macrocyclic tetranuclear oxidovanadium(V) compound, [(VVO)(L)(CH3O)]4, having coordinated four Schiff base (H2L) ligands, 3-methoxysalicylidenvaline. We showed that [(VVO)(L)(CH3O)]4: (i) has pH-dependent stability in biological media, (ii) binds to albumin in a dose-dependent manner, (iii) is taken up by cells in a time-dependent way, (iv) has a higher capacity to induce cell death compared to cisplatin (IC50 = 6 μM vs. 10 μM), by altering the oxidative and mitochondrial status in HepG2 cells. Unlike cisplatin, which blocks the cell cycle in the S-phase, the new vanadium-based compound arrests it in S and G2/M-phase, whereas no differences in the induction of DNA fragmentation and reduction of β-Tubulin synthesis between the two were determined. Thus, the [(VVO)(L)(CH3O)]4 antitumor mechanism involved corroboration between the generation of oxidative species, mitochondrial dysfunction, degradation of DNA, cell cycle arrest in the S and G2/M-phase, and β-Tubulin synthesis reduction. Our studies demonstrate the potent antitumor activity of [(VVO)(L)(CH3O)]4 and propose it as an attractive candidate for anticancer therapy.

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A comprehensive review on 3D tissue models: Biofabrication technologies and preclinical applications

Xie,

Pal,

et al. 2024

Biomaterials

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A novel platform for drug testing: Biomimetic three-dimensional hyaluronic acid-based scaffold seeded with human hepatocarcinoma cells

Cited by 26 publications

References 49 publications

Development of Dextran-Coated Magnetic Nanoparticles Loaded with Protocatechuic Acid for Vascular Inflammation Therapy

Development of Dextran-Coated Magnetic Nanoparticles Loaded with Protocatechuic Acid for Vascular Inflammation Therapy

Antitumor Properties of a New Macrocyclic Tetranuclear Oxidovanadium(V) Complex with 3-Methoxysalicylidenvaline Ligand

A comprehensive review on 3D tissue models: Biofabrication technologies and preclinical applications

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