scholarly journals SI-ATRP Decoration of Magnetic Nanoparticles with PHEMA and Post-Polymerization Modification with Folic Acid for Tumor Cells’ Specific Targeting

2021 ◽  
Vol 23 (1) ◽  
pp. 155
Author(s):  
Razvan Ghiarasim ◽  
Natalia Simionescu ◽  
Adina Coroaba ◽  
Cristina M. Uritu ◽  
Narcisa Laura Marangoci ◽  
...  
Keyword(s):  
Folic Acid ◽  
Magnetic Nanoparticles ◽  
Tumor Cells ◽  
High Specificity ◽  
The Body ◽  
Tumor Cell Lines ◽  
Resonance Imaging ◽  
Folate Receptors ◽  
Specific Targeting ◽  
Mcf 7

Targeted nanocarriers could reach new levels of drug delivery, bringing new tools for personalized medicine. It is known that cancer cells overexpress folate receptors on the cell surface compared to healthy cells, which could be used to create new nanocarriers with specific targeting moiety. In addition, magnetic nanoparticles can be guided under the influence of an external magnetic field in different areas of the body, allowing their precise localization. The main purpose of this paper was to decorate the surface of magnetic nanoparticles with poly(2-hydroxyethyl methacrylate) (PHEMA) by surface-initiated atomic transfer radical polymerization (SI-ATRP) followed by covalent bonding of folic acid to side groups of the polymer to create a high specificity magnetic nanocarrier with increased internalization capacity in tumor cells. The biocompatibility of the nanocarriers was demonstrated by testing them on the NHDF cell line and folate-dependent internalization capacity was tested on three tumor cell lines: MCF-7, HeLa and HepG2. It has also been shown that a higher concentration of folic acid covalently bound to the polymer leads to a higher internalization in tumor cells compared to healthy cells. Last but not least, magnetic resonance imaging was used to highlight the magnetic properties of the functionalized nanoparticles obtained.

Folic acid-conjugated polyethylene glycol-coated magnetic nanoparticles for doxorubicin delivery in cancer chemotherapy: Preparation, characterization and cytotoxicity on HeLa cell line

2016 ◽  
Vol 36 (8) ◽  
pp. 833-845 ◽  
Author(s):  
M Erdem ◽  
S Yalcin ◽  
U Gunduz
Keyword(s):  
Folic Acid ◽  
Polyethylene Glycol ◽  
Magnetic Nanoparticles ◽  
Cancer Chemotherapy ◽  
Hela Cells ◽  
The Body ◽  
Hela Cell Line ◽  
Conventional Chemotherapy ◽  
Cytotoxic Effects ◽  
Acidic Conditions

Conventional chemotherapy is the most valid method to cope with cancer; however, it has serious drawbacks such as decrease in production of blood cells or inflammation of the lining of the digestive tract. These side effects occur since generally the drugs used in chemotherapy are distributed evenly within the body of the patient and cannot distinguish the cancer cells from the healthy ones. In this study, folic acid (FA)-conjugated, polyethylene-coated magnetic nanoparticles (FA-MNPs), and doxorubicin (Dox)-loaded formulation (Dox-FA-MNPs) were prepared. The cytotoxicity of these nanoparticles on HeLa and Dox-resistant HeLa cells was investigated. Magnetic nanoparticles (MNPs), polyethylene glycol (PEG)-coated MNPs (PEG-MNPs), and FA-MNPs were successfully synthesized and characterized by several methods. Dox loading of FA-MNPs and release profile of Dox from the nanoparticles were studied. Cytotoxic effects of FA-MNPs and Dox-FA-MNPs on HeLa cells were analyzed. MNPs, PEG-MNPs, and FA-MNPs all had small sizes and supermagnetic behavior. High amounts of Dox could be loded onto the nanoparticles (290 μgmL−1). In 24 h, 15.7% of Dox was released from the Dox-FA-MNPs. The release was increased in acidic conditions (pH 4.1). Internalization studies showed that FA-MNPs and Dox-FA-MNPs were taken up efficiently by HeLa cells. The investigation of cytotoxicity of the particles indicated that 38–500 μgmL−1 Dox-FA-MNPs significantly decreased the proliferation of HeLa cells compared to FA-MNPs. Due to their size, magnetic properties, internalization, drug release, and cytotoxicity characteristics, the MNPs prepared in this study may have potential application as a drug delivery system in cancer chemotherapy.

Interaction of Human Tumor Cells with Human Platelets and the Coagulation System

1983 ◽  
Vol 50 (03) ◽  
pp. 726-730 ◽  
Author(s):  
Hamid Al-Mondhiry ◽  
Virginia McGarvey ◽  
Kim Leitzel
Keyword(s):  
Tumor Cell ◽  
Tumor Cells ◽  
Cell Lines ◽  
Human Tumor ◽  
Human Platelets ◽  
Factor Vii ◽  
Coagulation System ◽  
Breast Adenocarcinoma ◽  
Activate Factor ◽  
Tumor Cell Lines

SummaryThis paper reports studies on the interaction between human platelets, the plasma coagulation system, and two human tumor cell lines grown in tissue culture: Melanoma and breast adenocarcinoma. The interaction was monitored through the use of 125I- labelled fibrinogen, which measures both thrombin activity generated by cell-plasma interaction and fibrin/fibrinogen binding to platelets and tumor cells. Each tumor cell line activates both the platelets and the coagulation system simultaneously resulting in the generation of thrombin or thrombin-like activity. The melanoma cells activate the coagulation system through “the extrinsic pathway” with a tissue factor-like effect on factor VII, but the breast tumor seems to activate factor X directly. Both tumor cell lines activate platelets to “make available” a platelet- derived procoagulant material necessary for the conversion of prothrombin to thrombin. The tumor-derived procoagulant activity and the platelet aggregating potential of cells do not seem to be inter-related, and they are not specific to malignant cells.

Recent Advances on Therapeutic Peptides for Breast Cancer Treatment

2020 ◽  
Vol 21 ◽  
Author(s):  
Samad Beheshtirouy ◽  
Farhad Mirzaei ◽  
Shirin Eyvazi ◽  
Vahideh Tarhriz
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Breast Cancer Cells ◽  
Specific Binding ◽  
High Specificity ◽  
The Novel ◽  
Anti Cancer ◽  
Therapeutic Peptides ◽  
Low Toxicity

: Breast cancer is a heterogeneous malignancy which is the second cause of mortality among women in the world. Increasing the resistance to anti-cancer drugs in breast cancer cells persuades researchers to search the novel therapies approaches for the treatment of the malignancy. Among the novel methods, therapeutic peptides which target and disrupt tumor cells have been of great interest. Therapeutic peptides are short amino acids monomer chains with high specificity to bind and modulate a protein interaction of interest. Several advantages of peptides such as specific binding on tumor cells surface, low molecular weight and low toxicity on normal cells make the peptides as an appealing therapeutic agents against solid tumors, particularly breast cancer. Also, National Institutes of Health (NIH) describes therapeutic peptides as suitable candidate for the treatment of drug-resistant breast cancer. In this review, we attempt to review the different therapeutic peptides against breast cancer cells which can be used in treatment and diagnosis of the malignancy. Meanwhile, we presented an overview of peptide vaccines which have been developed for the treatment of breast cancer.

Specific Targeting of HER2-Positive Head and Neck Squamous Cell Carcinoma Line HN5 by Idarubicin-ZHER2 Affibody Conjugate

2018 ◽  
Vol 19 (1) ◽  
pp. 65-73 ◽  
Author(s):  
Marzieh Ghanemi ◽  
Aminollah Pourshohod ◽  
Mohammad Ali Ghaffari ◽  
Alireza kheirollah ◽  
Mansour Amin ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Line ◽  
Squamous Cell ◽  
Optimum Concentration ◽  
Her2 Positive ◽  
Affibody Molecules ◽  
Specific Targeting ◽  
Mcf 7

Background:Expression of human epidermal growth factor receptor type 2 (HER2) in head and neck squamous cell carcinoma (HNSCC) cell line HN5 can be employed with great opportunities of success for specific targeting of anti-cancer chemotherapeutic agents.Objective:In the current study, HER2-specific affibody molecule, ZHER2:342 (an engineered protein with great affinity for HER2 receptors) was selected for conjugation to idarubicin (an anti-neoplastic antibiotic).Method:ZHER2:342 affibody gene with one added cysteine code at the its 5′ end was synthesized de novo and then inserted into pET302 plasmid and transferred to E. Coli BL21 hosting system. After induction of protein expression, the recombinant ZHER2 affibody molecules were purified using Ni- NTA resin and purity was analyzed through SDS-PAGE. Affinity-purified affibody molecules were conjugated to idarubicin through a heterobifunctional crosslinker, sulfosuccinimidyl 4-(Nmaleimidomethyl) cyclohexane-1-carboxylate (Sulfo-SMCC). Specific toxicity of idarubicin-ZHER2 affibody conjugate against two HER2-positive cells, HN5 and MCF-7 was assessed through MTT assay after an exposure time of 48 hours with different concentrations of conjugate.Results:Idarubicin in the non-conjugated form showed potent toxic effects against both cell lines, while HN5 cells were significantly more sensitive compared to MCF-7 cells. Dimeric ZHER2 affibody showed a mild decreasing effect on growth of both HN5 and MCF-7 cells at optimum concentration. Idarubicin-ZHER2 affibody conjugate at an optimum concentration reduced viability of HN5 cell line more efficiently compared to MCF-7 cell line.In conclusion, idarubicin-ZHER2 affibody conjugate in optimum concentrations can be used for specific targeting and killing of HN5 cells.

Design, Synthesis and Antitumor Assessment of Phenylureas Bearing 5-Fluoroindolin-2-one Moiety

2020 ◽  
Vol 16 (7) ◽  
pp. 958-968
Author(s):  
Yunrui Cai ◽  
Tong Chen ◽  
Huajian Zhu ◽  
Hongbin Zou
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Human Cancer ◽  
The Body ◽  
Human Breast ◽  
Design Synthesis ◽  
Human Carcinoma ◽  
Xenograft Models ◽  
New Compounds ◽  
Mcf 7

Background: The development of novel antineoplastic agents remains highly desirable. Objective: This study focuses on the design, synthesis, and antitumor evaluation of phenyl ureas bearing 5-fluoroindolin-2-one moiety. Methods: Three sets of phenylureas were designed and synthesized and their antiproliferative ability was measured against four human carcinoma cell lines (Hela, Eca-109, A549, and MCF-7) via MTT assay. In vivo anticancer activity was further evaluated in xenograft models of human breast cancer (MCF-7). Results: A total of twenty-one new compounds were synthesized and characterized by means of 1H and 13C NMR as well as HR-MS. Three sets of compounds (1a‒1c, 2a‒2c, and 3a‒3c) were initially constructed, and preliminary antiproliferative activities of these molecules were evaluated against Hela, Eca-109, A549 and MCF-7, highlighting the meta-substituted phenylureas (1a‒1c) as the most cytotoxic set. A series of meta-substituted phenylureas derivatives (1d‒1o) were then designed and synthesized for structure-activity relationship study. Most of the new compounds showed desirable cytotoxicity, among which compound 1g exhibited the most remarkable cytotoxic effects against the tested human cancer cells with IC50 values ranging from 1.47 to 6.79 μM. Further studies showed that compound 1g suppressed tumor growth in human breast cancer (MCF- 7) xenograft models without affecting the body weight of its recipients. Conclusion: In this study, twenty-one new compounds, containing the privileged structures of phenylurea and 5-fluoroindolin-2-one, were designed and synthesized. Subsequent structureactivity studies showed that 1g was the most bioactive antitumor agent among all tested compounds, hence a potentially promising lead compound once given further optimization.

Co-delivery of Doxorubicin and D-α-Tocopherol Polyethylene Glycol 1000 Succinate by Magnetic Nanoparticles

2018 ◽  
Vol 18 (8) ◽  
pp. 1138-1147 ◽  
Author(s):  
Esra Metin ◽  
Pelin Mutlu ◽  
Ufuk Gündüz
Keyword(s):  
Breast Cancer ◽  
Polyethylene Glycol ◽  
Magnetic Nanoparticles ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Drug Loading ◽  
Gravimetric Analysis ◽  
Polyethylene Glycol 1000 ◽  
Mcf 7

Background: Although conventional chemotherapy is the most common method for cancer treatment, it has several side effects such as neuropathy, alopecia and cardiotoxicity. Since the drugs are given to body systemically, normal cells are also affected, just like cancer cells. However, in recent years, targeted drug delivery has been developed to overcome these drawbacks. Objective: The aim of this study was targeted co-delivery of doxorubicin (Dox) which is an anticancer agent and D-α-Tocopherol polyethylene glycol 1000 succinate (vitamin E TPGS or simply TPGS) to breast cancer cells. For this purpose, Magnetic Nanoparticles (MNPs) were synthesized and coated with Oleic Acid (OA). Coated nanoparticles were encapsulated in Poly Lactic-co-Glycolic Acid (PLGA) and TPGS polymers and loaded with Dox. The Nanoparticles (NPs) were characterized by Fourier Transform Infrared (FTIR) spectroscopy, zetapotential analysis, Dynamic Light Scattering (DLS) analysis, Thermal Gravimetric Analysis (TGA) and Scanning Electron Microscope (SEM) analysis. Results: The results showed that NPs were spherical, superparamagnetic and in the desired range for use in drug targeting. The targetability of NPs was confirmed. Moreover, TPGS and Dox loading was shown by TGA and FTIR analyses. NPs were internalized by cells and the cytotoxic effect of drug loaded NPs on sensitive (MCF-7) and drug-resistant (MCF-7/Dox) cells were examined. It was seen that the presence of TPGS increased cytotoxicity significantly. TPGS also enhanced drug loading efficiency, release rate, cellular internalization. In MCF- 7/Dox cells, the drug resistance seems to be decreased when Dox is loaded onto TPGS containing NPs. Conclusion: This magnetic PLGA nanoparticle system is important for new generation targeted chemotherapy and could be used for breast cancer treatment after in vivo tests.

Shaping and Cellular Uptake of Folic Acid Coated Gold and Magnetite Nanoparticles

2019 ◽  
Vol 9 (2) ◽  
pp. 166-172
Author(s):  
Ahmed A.G. El-Shahawy ◽  
Gamal Elghnam ◽  
Alsayed A.M. Alsherbini
Keyword(s):  
Folic Acid ◽  
Iron Oxide ◽  
Tumor Cells ◽  
Iron Oxide Nanoparticles ◽  
Individual Cell ◽  
Oxide Nanoparticles ◽  
Cellular Compartment ◽  
Specific Tumor ◽  
Uv Visible

Background:Gold and Iron Oxide nanoparticles NPs play as nanocarriers for a specific drug delivery and contrast agents. Intercellular uptake of these nanoparticles and targeting to individual cell and sub-cellular compartment is essential.Objective:The aim of the current study is to evaluate the intracellular uptake of these NPs to specific tumor cells in vitro conjugated with folic acid with a goal of enhancing the efficiency of specific targeting to tumor cells.Methods:We synthesized the nanoparticles by a chemical method and characterized by UV-Visible, FTIR, XRD, and TEM.Results & Conclusion:The results revealed the conjugation of Gold and Iron Oxide nanoparticles with folic acid increased the intercellular uptake with high percent compared to non- conjugated nanoparticles.

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