scholarly journals In vitro/ In vivo Electrochemical Detection of Pt(II) Species

2021 ◽  
Author(s):  
Alexander Vaneev ◽  
Petr Gorelkin ◽  
Olga Krasnovskaya ◽  
Roman Akasov ◽  
Daniil Spector ◽  
...  
Keyword(s):  
Electrochemical Detection ◽  
Single Cells ◽  
Electrochemical Technique ◽  
Breast Adenocarcinoma ◽  
Tumor Spheroids ◽  
Tumor Bearing ◽  
Advanced Tumor ◽  
Mcf 7

The biodistribution of chemotherapy compounds within tumor tissue is one of the main challenges in the development of antineoplastic drugs, and novel techniques for simple, non-expensive, sensitive, and selective detection of various analytes in tumors are of great importance. In this paper we propose the use of platinized carbon nanoelectrodes (PtNE) for electrochemical detection of platinum-based drugs in various biological models, including single cells and tumor spheroids in vitro, and inside solid tumors in vivo. We have demonstrated quantitative direct detection of Pt(II) in breast adenocarcinoma MCF-7 cells treated with cisplatin and cisplatin-based DNP prodrug. To realize the potential of this technique in advanced tumor models, we measured Pt(II) in 3D tumor spheroids in vitro and tumor-bearing mice in vivo. The concentration gradient of Pt (II) species correlated with the distance from the sample surface in MCF-7 tumor spheroids. We then performed detection of Pt(II) species in tumor-bearing mice treated intravenously with cisplatin and DNP. We found that there was deeper penetration of DNP in comparison to cisplatin. This research demonstrates a novel minimally invasive, real-time electrochemical technique for the study of platinum-based drugs.

scholarly journals Amphiphilic Poly(N-vinylpyrrolidone) Nanoparticles Conjugated with DR5-Specific Antitumor Cytokine DR5-B for Targeted Delivery to Cancer Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1413
Author(s):  
Anne Yagolovich ◽  
Andrey Kuskov ◽  
Pavel Kulikov ◽  
Leily Kurbanova ◽  
Dmitry Bagrov ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
In Vitro Cytotoxicity ◽  
Breast Adenocarcinoma ◽  
Hydrophobic Core ◽  
Tumor Spheroids ◽  
Wide Range ◽  
Therapeutic Molecules ◽  
Mcf 7

Nanoparticles based on the biocompatible amphiphilic poly(N-vinylpyrrolidone) (Amph-PVP) derivatives are promising for drug delivery. Amph-PVPs self-aggregate in aqueous solutions with the formation of micellar nanoscaled structures. Amph-PVP nanoparticles are able to immobilize therapeutic molecules under mild conditions. As is well known, many efforts have been made to exploit the DR5-dependent apoptosis induction for cancer treatment. The aim of the study was to fabricate Amph-PVP-based nanoparticles covalently conjugated with antitumor DR5-specific TRAIL (Tumor necrosis factor-related apoptosis-inducing ligand) variant DR5-B and to evaluate their in vitro cytotoxicity in 3D tumor spheroids. The Amph-PVP nanoparticles were obtained from a 1:1 mixture of unmodified and maleimide-modified polymeric chains, while DR5-B protein was modified by cysteine residue at the N-end for covalent conjugation with Amph-PVP. The nanoparticles were found to enhance cytotoxicity effects compared to those of free DR5-B in both 2D (monolayer culture) and 3D (tumor spheroids) in vitro models. The cytotoxicity of the nanoparticles was investigated in human cell lines, namely breast adenocarcinoma MCF-7 and colorectal carcinomas HCT116 and HT29. Notably, DR5-B conjugation with Amph-PVP nanoparticles sensitized resistant multicellular tumor spheroids from MCF-7 and HT29 cells. Taking into account the nanoparticles loading ability with a wide range of low-molecular-weight antitumor chemotherapeutics into hydrophobic core and feasibility of conjugation with hydrophilic therapeutic molecules by click chemistry, we suggest further development to obtain a versatile system for targeted drug delivery into tumor cells.

Synthesis and In Vitro Anticancer Activity of 6-Ferrocenylpyrimidin-4(3H)-one Derivatives

2019 ◽  
Vol 16 (1) ◽  
pp. 160-164 ◽  
Author(s):  
Stanislav A. Grabovskiy ◽  
Rinat S. Muhammadiev ◽  
Lenar R. Valiullin ◽  
Ivan S. Raginov ◽  
Natalie N. Kabal'nova
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Practical Interest ◽  
Breast Adenocarcinoma ◽  
Human Skin Fibroblast ◽  
Normal Human Skin ◽  
Normal Human ◽  
Mcf 7

Aim and Objective: Some ferrocenyl derivatives are active in vitro and in vivo against cancer. Generally, ferrocenyl derivatives for cancer research have three key components: a ferrocene moiety, a conjugated linker that lowers the oxidation potential and some derivative (peptide, nucleobase and others) that can interact with biomolecules. Since the pyrimidine fragment can easily pass through the membrane into the cells and become involved in metabolism; it appears to be promising. Furthermore, this fragment is an electron-acceptor group, so a spacer can be excluded. Therefore, the synthesis of 6-ferrocenylpyrimidin-4(3H)-one derivatives and the study of their anticancer activity have scientific and practical interest. </P><P> Methods: The syntheses of 6-ferrocenylpyrimidin-4(3H)-one derivatives were performed by the condensation of ethyl 3-ferrocenyl-3-oxopropionate with thiourea or acetamidine or guanidine. The cytotoxicity of four 6- ferrocenylpyrimidin-4(3H)-one derivatives was evaluated by using the MTT assay in vitro against Human breast adenocarcinoma MCF-7 and normal human skin fibroblast HSF cells. The tested derivatives induced a concentration-dependent cytotoxic response in cell lines. </P><P> Results: A study of the cytotoxic activity of 6-ferrocenylpyrimidin-4(3H)-one derivatives by the MTT test has found that all compounds have a dose-dependent toxic effect on the lines of breast cancer cells (MCF-7) and normal human fibroblast cells (HSF). The most pronounced cytotoxic effect is exhibited by 2-methyl-6-ferrocenylpyrimidin- 4(3H)-one (MCF-7, IC50 17 ± 1 µM). Conclusion: The experimental results confirm the importance of investigation and design of ferrocenylpyrimidin- 4(3H)-one derivatives as anticancer agents. Compounds where the pyrimidine derivatives are directly linked to the ferrocene unit rather than via a spacer group also may be of interest for antiproliferative drug design.

scholarly journals A Novel Radioimmune 99mTc-Labeled Tracer for Imaging Sphingosine 1-Phosphate Receptor 1 in Tumor Xenografts: An In Vitro and In Vivo Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Min Ye ◽  
Yongkang Gai ◽  
Hao Ji ◽  
Yaqun Jiang ◽  
Pengxin Qiao ◽  
...  
Keyword(s):  
Biological Activities ◽  
Photon Emission ◽  
Cell Uptake ◽  
Emission Computed Tomography ◽  
Tumor Bearing ◽  
Study Results ◽  
Sphingosine 1 Phosphate ◽  
Mcf 7

Sphingosine-1-phosphate (S1P) is a phospholipid that regulates pleiotropic biological activities and exerts extracellular functions by binding to five specific G-protein-coupled receptors, S1P receptors (S1PR) 1–5. When activated by S1P, S1PR promote the proliferation and invasion of tumor cells by inducing the formation of new blood vessels. We developed and assessed a new monoclonal antibody imaging probe 99mTc-HYNIC-S1PR1mAb, to explore the feasibility of targeting the S1PR1 in vitro and in vivo. S1PR1mAb was prepared and followed by technetium-99m labeling with succinimidyl 6-hydraziniumnicotinate hydrochloride. Cell uptake and blocking studies were performed to investigate the binding specificity of 99mTc-HYNIC-S1PR1mAb in vitro. 99mTc-HYNIC-S1P1mAb was also tested in vivo in mice xenografted with SK-HEP-1 (high-expression of S1PR1) and MCF-7 (low-expression of S1PR1) using single-photon emission-computed tomography (SPECT). Ex vivo gamma counting of tissues from tumor-bearing mice was used to evaluate 99mTc-HYNIC-S1PR1mAb biodistribution. The biodistribution study results showed significantly higher uptake in SK-HEP-1 tumors than in MCF-7 tumors (P &lt; 0.001). Reduced uptake of 99mTc-HYNIC-S1PR1mAb in SK-HEP-1 was observed in tumor-bearing nude mice pretreated with fingolimod, which binds competitively to the receptors, especially S1PR1. 99mTc-HYNIC-S1PR1mAb can be synthesized and specifically targeted to S1PR1 in vitro and in vivo, allowing S1PR1 expression assessment with SPECT imaging.

scholarly journals Two-pronged anti-tumor therapy by a new polymer-paclitaxel conjugate micelle with an anti-multidrug resistance effect

2021 ◽  
Author(s):  
Juan Du ◽  
Lanlan Zong ◽  
Mengmeng Li ◽  
Yonghui Qiao ◽  
Keke Yu ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Human Life ◽  
Tumor Therapy ◽  
Subcutaneous Tumor ◽  
Tumor Bearing ◽  
In Vivo Experiments ◽  
Alternative Delivery ◽  
Mcf 7

Abstract Cancerous tumors are still a major disease that threatens human life, with tumor multidrug resistance (MDR) being one of the main reasons for the failure of chemotherapy. Here, a reduction-sensitive polymer prodrug micelle, mPEG-DCA-SS-PTX (PDSP), was manufactured with a new polymer inhibitor of drug-resistance as a carrier to overcome MDR and improve the anti-tumor effect of paclitaxel (PTX). The PDSP micelles display good stability, double-responsive drug release, and excellent biocompatibility. The PDSP micelles reduced the cytotoxicity of PTX to normal HL-7702 cells, and enhanced that to SMMC-7721 and MCF-7 cells in vitro. Improved sensitivity of A549/ADR to PDSP was also observed in vitro. Furthermore, in vivo experiments show reduced systemic toxicity and enhanced therapeutic efficacy of DOX to H22 subcutaneous tumor-bearing mice. This work proves the reduction sensitive polymer prodrug micelles carried by the new polymer inhibitor can be used as an alternative delivery system to target tumors and reverse MDR for paclitaxel and other tumor-resistant drugs.

scholarly journals In vitro and in vivo matrix metalloproteinase expression after photodynamic therapy with a liposomal formulation of aminolevulinic acid and its methyl ester

2010 ◽  
Vol 15 (4) ◽  
Author(s):  
Beata Osiecka ◽  
Kamil Jurczyszyn ◽  
Krzysztof Symonowicz ◽  
Andrzej Bronowicz ◽  
Paweł Ostasiewicz ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Methyl Ester ◽  
Tumor Cells ◽  
Aminolevulinic Acid ◽  
Malignant Tumors ◽  
Single Cells ◽  
Liposomal Formulation ◽  
Tumor Bearing

AbstractPhotodynamic therapy (PDT) is a well-known method for the treatment of malignant tumors, and its principles have been well established over the past 30 years. This therapy involves the application of a chemical called a photosensitizer and its subsequent excitation with light at the appropriate wavelength and energy. Topical photodynamic therapy with aminolevulinic acid (5-ALA) is an alternative therapy for many malignant processes, including nonmelanoma skin cancers such as basal-cell carcinoma (BCC). Our novel approach for this study was to use a liposomal formulation of 5-ALA and its methyl ester (commercially available as metvix) both in vitro and in vivo, and to check whether the liposome-entrapped precursors of photosensitizers can induce the expression of metalloproteinases (MMPs) in animal tumor cells and in other tissues from tumor-bearing rats and in selected cell lines in vitro. We also checked whether the application of tissue inhibitors of matrix metalloproteinases (TIMPs) has any effect on MMPs in the above-mentioned experimental models, and if they can cause complete inhibition of MMP expression. Immunohistochemical studies revealed that after the PDT, the intensity of expression of MMPs in healthy animals was very low and seen in single cells only. After the PDT in tumor-bearing rats, MMP-3 was expressed in the tumor cells with the highest intensity of staining in the tissues directly adjacent to the tumors, while MMP-2 and -9 were not found. In the control groups, there was no observed expression of MMPs. In vitro studies showed that MMP-3 was expressed in MCF-7 cells after PDT, but MMP-9 was not observed and MMP-2 was only seen in single cases. Our studies confirmed that the application of an MMP-3 inhibitor may block an induction of MMP-3 expression which had previously been initiated by PDT. The preliminary data obtained from cancer patients revealed that new precursors are effective in terms of PDT, and that using MMP inhibitors should be considered as a potential enhancing factor in clinical PDT.

A Novel Triazole Derivative Drug Presenting In Vitro and In Vivo Anticancer Properties

2018 ◽  
Vol 18 (17) ◽  
pp. 1483-1493
Author(s):  
Ricardo Imbroisi Filho ◽  
Daniel T.G. Gonzaga ◽  
Thainá M. Demaria ◽  
João G.B. Leandro ◽  
Dora C.S. Costa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Hepatic Function ◽  
Anticancer Properties ◽  
Mcf 7

Background: Cancer is a major cause of death worldwide, despite many different drugs available to treat the disease. This high mortality rate is largely due to the complexity of the disease, which results from several genetic and epigenetic changes. Therefore, researchers are constantly searching for novel drugs that can target different and multiple aspects of cancer. Experimental: After a screening, we selected one novel molecule, out of ninety-four triazole derivatives, that strongly affects the viability and proliferation of the human breast cancer cell line MCF-7, with minimal effects on non-cancer cells. The drug, named DAN94, induced a dose-dependent decrease in MCF-7 cells viability, with an IC50 of 3.2 ± 0.2 µM. Additionally, DAN94 interfered with mitochondria metabolism promoting reactive oxygen species production, triggering apoptosis and arresting the cancer cells on G1/G0 phase of cell cycle, inhibiting cell proliferation. These effects are not observed when the drug was tested in the non-cancer cell line MCF10A. Using a mouse model with xenograft tumor implants, the drug preventing tumor growth presented no toxicity for the animal and without altering biochemical markers of hepatic function. Results and Conclusion: The novel drug DAN94 is selective for cancer cells, targeting the mitochondrial metabolism, which culminates in the cancer cell death. In the end, DAN94 has been shown to be a promising drug for controlling breast cancer with minimal undesirable effects.

Evaluation of Cytotoxic and Tyrosinase Inhibitory Activities of 2-phenoxy(thiomethyl) pyridotriazolopyrimidines: In Vitro and Molecular Docking Studies

2020 ◽  
Vol 20 (14) ◽  
pp. 1714-1721
Author(s):  
Hatem A. Abuelizz ◽  
El Hassane Anouar ◽  
Mohamed Marzouk ◽  
Mizaton H. Hasan ◽  
Siti R. Saleh ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Kojic Acid ◽  
Docking Studies ◽  
Breast Adenocarcinoma ◽  
Amino Acid Residues ◽  
New Class ◽  
Structure Activity ◽  
Tyrosinase Inhibitors ◽  
Mcf 7

Background: The use of tyrosinase has confirmed to be the best means of recognizing safe, effective, and potent tyrosinase inhibitors for whitening skin. Twenty-four 2-phenoxy(thiomethyl)pyridotriazolopyrimidines were synthesized and characterized in our previous studies. Objective: The present work aimed to evaluate their cytotoxicity against HepG2 (hepatocellular carcinoma), A549 (pulmonary adenocarcinoma), MCF-7 (breast adenocarcinoma) and WRL 68 (embryonic liver) cell lines. Methods: MTT assay was employed to investigate the cytotoxicity, and a tyrosinase inhibitor screening kit was used to evaluate the Tyrosinase (TYR) inhibitory activity of the targets. Results: The tested compounds exhibited no considerable cytotoxicity, and nine of them were selected for a tyrosinase inhibitory test. Compounds 2b, 2m, and 5a showed good inhibitory percentages against TYR compared to that of kojic acid (reference substance). Molecular docking was performed to rationalize the Structure-Activity Relationship (SAR) of the target pyridotriazolopyrimidines and analyze the binding between the docked-selected compounds and the amino acid residues in the active site of tyrosinase. Conclusion: The target pyridotriazolopyrimidines were identified as a new class of tyrosinase inhibitors.

Derivatives of Deoxypodophyllotoxin Induce Apoptosis Through Bcl-2/Bax Proteins Expression

2020 ◽  
Vol 20 ◽  
Author(s):  
Ya-Nan Li ◽  
Ni Ning ◽  
Lei Song ◽  
Yun Geng ◽  
Jun-Ting Fan ◽  
...  
Keyword(s):  
Annexin V ◽  
Mtt Method ◽  
Anthriscus Sylvestris ◽  
Anti Tumor Activity ◽  
Derivatives Of ◽  
Toxicity In Vitro ◽  
Ht 29 ◽  
Mcf 7

Background: Deoxypodophyllotoxin, isolated from theTraditional Chinese Medicine Anthriscus sylvestris, is well-known because of its significant antitumor activity with strong toxicity in vitro and in vivo. Objective: In this article, we synthesized a series of deoxypodophyllotoxin derivatives, and evaluated their antitumor effectiveness.Methods:The anti tumor activity of deoxypodophyllotoxin derivatives was investigated by the MTT method. Apoptosis percentage was measured by flow cytometer analysis using Annexin-V-FITC. Results: The derivatives revealed obvious cytotoxicity in the MTT assay by decreasing the number of late cancer cells. The decrease of Bcl-2/Bax could be observed in MCF-7, HepG2, HT-29 andMG-63 using Annexin V-FITC. The ratio of Bcl-2/Bax in the administration group was decreased, which was determined by the ELISA kit. Conclusion: The derivatives of deoxypodophyllotoxin could induce apoptosis in tumor cell lines by influencing Bcl-2/Bax.

Sign in / Sign up

Export Citation Format

Share Document