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7. Asialoglycoprotein Receptor Targeted Magnetic Nanoparticles For Hepatocellular Carcinoma Treatment.

Author

Karakayali, Tugba, Erek, Ayca, Ak, Guliz, and Sanlier, Senay

Subjects
ASIALOGLYCOPROTEIN receptors, HEPATOCELLULAR carcinoma, MAGNETIC nanoparticles, DRUG delivery systems, DOXORUBICIN
Abstract

Objective: Hepatocellular carcinoma is the most common type of liver cancer. Doxorubicin (Dox) is an anthracycline antibiotic and is commonly used for cancer treatment. However, Dox has severe side effects that limit efficiency, and it is used with drug delivery systems. Asialoglycoprotein receptors are membrane glycoprotein receptors and are expressed in hepatocellular carcinoma. This study, it is aimed to develop a magnetic field and asialoglycoprotein receptor-targeted, doxorubicin-loaded nanoparticle system to be used in the treatment of hepatocellular carcinoma. Research methods: Magnetic nanoparticles were synthesized by the co-precipitation method. The surface was functionalized with 2-aminoethylphosphonic acid to provide the binding of arabinogalactan with magnetic nanoparticles. Then, MNP's surface was coated with arabinogalactan. After that, doxorubicin was loaded on arabinogalactan-coated magnetic nanoparticles by adsorption. The functional groups, hydrodynamic size, zeta potential, and drug encapsulation efficiency were evaluated. Results and Conclusion: The SEM size of the Dox-loaded arabinogalactan-coated magnetic nanoparticle(DANP) was found to be 30-35 nm. FTIR analysis has confirmed the presence of doxorubicin on arabinogalactan-coated ANPs. Dox loading efficiency was determined as 78.54 %. Based on the results obtained, the study is thought to have potential for in vitro, in vivo, and ex vivo studies. [ABSTRACT FROM AUTHOR]

Published
2021

8. Investigation of the Potential In Vitro Usage of Asialoglycoprotein Receptor Targeted Magnetic Nanoparticles for Hepatocellular Carcinoma.

Author

Erek, Ayca, Karakayali, Tugba, Ak, Guliz, Oktay, Latife Merve, Gunel, Nur Selvi, and Sanlier, Senay

Subjects
ASIALOGLYCOPROTEIN receptors, MAGNETIC nanoparticles, HEPATOCELLULAR carcinoma, LIVER cells, DOXORUBICIN
Abstract

Objective: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. The World Health Organization stated that by 2030, the number of deaths from hepatocellular carcinoma would be more than 1 million. It is known that there is a high amount of asialoglycoprotein receptors (ASPGR) on the hepatocyte surface, and they are intensely expressed in HCC. These properties make ASGPR an attractive target for receptor-directed drug delivery to hepatocarcinoma cells. New drug delivery systems are being developed to prevent the side effects and limitations of commonly used treatment methods. As an antineoplastic agent, doxorubicin is used for the treatment of many cancers. Research methods: This study aimed to perform in vitro cytotoxicity and biocompatibility tests of the synthesized asialoglycoprotein receptor-targeted and doxorubicin carrying magnetic nanoparticles to treat HCC. For this purpose, after the synthesis of magnetic nanoparticles loaded with doxorubicin, serum protein binding and hemolysis were assayed. The cytotoxicity studies were carried out on hepatocellular carcinoma cell, HEPG2, and human epithelial liver cell, THLE-2. Results and Conclusion: The cytotoxicity studies were carried out on hepatocellular carcinoma cell, HEPG2, and human epithelial liver cell, THLE-2. According to the results, it was found that the prepared formulation was biocompatible, had no hemolytic effect, and created cytotoxicity in cancer cells. As a result, it is thought that the doxorubicin-loaded asialoglycoprotein targeted magnetic nanoparticle system has a high potential for use in the treatment of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Published
2021

9. Targeted Dual Therapy with Curcumin Encapsulated Liposomes for Treatment of Glioblastoma.

Author

Karadag, Belguzar, Ak, Guliz, Karakayali, Tugba, Gumustas, Baris, Ozmen, Gulce Danaci, and Sanlier, Senay

Subjects
CURCUMIN, GLIOBLASTOMA multiforme, BLOOD-brain barrier, POLYETHYLENE glycol, LIPOSOMES, CARMUSTINE
Abstract

Glioblastoma multiforme is one of the most aggressive brain tumors occurring in the central nervous system and should be treated immediately as it spreads very quickly. One of the most important limiting effects in treatment is the inability of the drug to cross the blood-brain barrier. In this situation, it is important to develop new treatment approaches for glioblastoma. In this study, carmustine, doxorubicin and curcumin-loaded, and polyethylene glycol coated liposomes were developed for efficient and targeted therapy of glioblastoma. As active components, carmustine is in the alkylating agent class, while curcumin is a herbal agent with a therapeutic effect. In addition, doxorubicin is used in many cancer treatments, including glioblastoma. First, a pre-emulsion was prepared using different lipids, and the lipid emulsion was passed through a microfluidic device to obtain liposomes. Empty liposomes were studied under the specified conditions and the hydrodynamic size, polydispersity index (PDI) of the samples were determined. Then, triple drug-loaded liposomes were prepared using diluted amounts of each drug, carmustine, doxorubicin, and curcumin. The encapsulation efficiency (%) of drugs was determined using HPLC analysis. The hydrodynamic size of the triple drug-loaded liposomes was 139.30±13.23 nm, and PDI value was 0.197±0.072. Finally, the surfaces of the liposomes were coated with DSPE-mPEG2000 to cross the blood-brain barrier. Liposomes were also characterized. Consequently, liposomes are predicted to have the potential for further in vitro and in vivo studies. [ABSTRACT FROM AUTHOR]

Published
2021

10. Synthesis of Methotrexate Loaded Chitosan Nanoparticles and in vitro Evaluation of the Potential in Treatment of Prostate Cancer

Author

Biray Avci Cigir, Kipcak Sezgi, Akgun Cansu, Yilmaz Habibe, Ozel Buket, Ak Güliz, Selvi Gunel Nur, Aktan Cagdas, Dodurga Yavuz, and Hamarat Sanlier Senay

Subjects
Cancer Research, cell viability assay, Cytotoxicity, clinical evaluation, Cell, IC50, Pharmacology, 030226 pharmacology & pharmacy, 01 natural sciences, chemistry.chemical_compound, 0302 clinical medicine, chitosan derivative, immune system diseases, skin and connective tissue diseases, comparative study, drug release, cell proliferation assay, 010304 chemical physics, nanoparticle, apoptosis, Methotrexate delivery, prostate cancer, medicine.anatomical_structure, Molecular Medicine, Trypan blue, musculoskeletal diseases, methotrexate, Article, nanoencapsulation, 03 medical and health sciences, 0103 physical sciences, LNCaP, medicine, controlled study, human, Viability assay, centrifugation, Cell growth, human cell, Chitosan nanoparticles, LNCaP cell line, In vitro, chemistry, Apoptosis, hydrodynamics, Immunology, drug synthesis
Abstract

The objective of the study was to investigate the cytotoxic and apoptotic effects of Methotrexate (MTX)-loaded chitosan (CS) on LNCaP prostate cancer cell line in vitro. For this purpose, CS nanoparticles (NPs) were synthesized through ionic gelation method and MTX was loaded into the carrier with encapsulation. SEM images of the CS NPs have revealed that they have size of about 85 nm in mono-disperse manner. Drug loading yield was found to be 95.7 % with 470 µg drug/mg NP loading capacity. In vitro drug release study showed that MTX was released in a controlled manner. Cell viability was detected by using trypan blue dye exclusion test and WST-1 cell proliferation assay was performed to show cytotoxic effects of the CS, the MTX and the MTX-loaded NP. IC50 values of CS, MTX and MTX-loaded NPs were assigned from the cell survival plot and were determined as 67.18 µM, 20.21 µM and 2.94 µM at the 72nd hour, respectively. As for apoptosis analysis results, following to MTX-loaded CS treatment of LNCAP cells, apoptotic cell percent was detected as 39.3 % at the 72nd hour, that is, MTX-loaded CS induces 1.85-fold increase in apoptotic cell percent in comparison with that of MTX- induced apoptosis. © 2016 Bentham Science Publishers.

Published
2016
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11. Development Of Ultrasound-Triggered And Magnetic-Targeted Nanobubble System For Dual-Drug Delivery

Author

Sanlier, Senay Hamarat, Ak, Guliz, Yilmaz, Habibe, Unal, Ayse, Bozkaya, Ummuhan Fulden, Taniyan, Gokce, Yildirim, Yeliz, and Turkyilmaz, Gulbeyaz Yildiz

Abstract

Non-small cell lung cancer (NSCLC) constitutes more than 85% of lung cancer case. Pemetrexed is used to treat types of NSCLC, and pazopanib is used for some types of soft tissue sarcoma. The aim of the study was development of pemetrexed and pazopanib carrying nanobubble system with magnetic responsiveness and ultrasound sensitivity properties for targeted NSCLC therapy. Drugs were linked to newly designed peptide, and peptide drug conjugates were attached to amine-modified magnetite. Resulting nanoparticles were encapsulated into liposomes, and liposomes were extruded, then nanobubble system was prepared. Moreover, nanobubble biodistribution was monitored by in vivo imaging system. As a result, based on high-performance liquid chromatography data, magnetite and peptide-pemetrexed were conjugated with 54.02% yield, and magnetite and peptide-pazopanib were bound with 63.53% yield. Hydrodynamic size of nanobubbles, prepared from liposomes filtered through 800 nm and 400 nm, was determined as 491.1 +/- 130.2 and 275.8 +/- 117.8 nm, respectively. Carrier system was accumulated into tumor area with 80.22% yield of the injected carrier system. It was found that nanobubbles were magnetic responsive for accumulation via magnetic field and could be disrupted by ultrasound via focused acoustic pressure, which lead to targeted drug delivery. These nanobubble systems could be investigated for intravenous and inhaler administration in further studies. (c) 2019 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.

Published
2019

14. Development Of Gemcitabine-Adsorbed Magnetic Gelatin Nanoparticles For Targeted Drug Delivery In Lung Cancer

Author

Sanlier, Senay Hamarat, Yasa, Merve, Cihnioglu, Asli Ozge, Abdulhayoglu, Merve, Yilmaz, Habibe, and Ak, Guliz

Abstract

Magnetic iron oxide nanoparticles (IONPs) were coated with gelatin type B by means of the two-step desolvation method. Drug loading by adsorption was studied under various conditions such as different temperature, contact time, pH, and initial gemcitabine concentration. Further, Langmuir isotherm curves were constracted and constants were calculated. According to the Langmuir isotherm, the Gibbs free energy of the adsorption process at 25 degrees C was - 4.74 kJ/mol. On the other hand, this value at 37 degrees C was - 7.86 kJ/mol. In vitro drug release was performed at pH levels of 5 and 7.4, with gemcitabine-loaded magnetic gelatin nanoparticles and free gemcitabine, and both the results were subsequently compared.

Published
2016

19. Synthesis of Methotrexate Loaded Chitosan Nanoparticles and in vitro Evaluation of the Potential in Treatment of Prostate Cancer

Author

Nur, Selvi, Buket, Ozel, Sezgi, Kipcak, Cagdas, Aktan, Cansu, Akgun, Guliz, Ak, Habibe, Yilmaz, Avci Cigir, Biray, Yavuz, Dodurga, and Sanlier Senay, Hamarat

Abstract

The objective of the study was to investigate the cytotoxic and apoptotic effects of Methotrexate (MTX)-loaded chitosan (CS) on LNCaP prostate cancer cell line in vitro. For this purpose, CS nanoparticles (NPs) were synthesized through ionic gelation method and MTX was loaded into the carrier with encapsulation. SEM images of the CS NPs have revealed that they have size of about 85 nm in mono-disperse manner. Drug loading yield was found to be 95.7 % with 470 μg drug/mg NP loading capacity. In vitro drug release study showed that MTX was released in a controlled manner. Cell viability was detected by using trypan blue dye exclusion test and WST-1 cell proliferation assay was performed to show cytotoxic effects of the CS, the MTX and the MTX-loaded NP. IC50 values of CS, MTX and MTX-loaded NPs were assigned from the cell survival plot and were determined as 67.18 μM, 20.21 μM and 2.94 μM at the 72nd hour, respectively. As for apoptosis analysis results, following to MTX-loaded CS treatment of LNCAP cells, apoptotic cell percent was detected as 39.3 % at the 72nd hour, that is, MTX-loaded CS induces 1.85-fold increase in apoptotic cell percent in comparison with that of MTX- induced apoptosis.

Published
2016

20. In vitro and in vivo evaluation of folate receptor-targeted a novel magnetic drug delivery system for ovarian cancer therapy

Author

Ak, Güliz, Yilmaz, Habibe, Güneş, Aybike, and Sanlier, Senay Hamarat

Subjects
3. Good health
Abstract

Doxorubicin is widely used anticancer drug; however, use of doxorubicin is limited. Under externally applied magnetic field, magnetic agents can help to transport drug directly to tumor. Folate receptor is overexpressed in ovarian carcinomas. In this study, we aimed to develop magnetically responsive and folate receptor-targeted biomimetic drug delivery system for ovarian cancer therapy. Doxorubicin-loaded and glucose/gluconic acid-coated magnetic nanoparticles were synthesized and erythrocyte membrane vesicles were used for coating of nanoparticles. Folate ligand was anchored to surface so as to target receptor. Hydrodynamic size of nanocarrier was found as 91.2 ± 20.8 nm. The results showed that delivery system has controlled drug release profile and biocompatible features. In folate-free medium, folate receptor-targeted nanocarrier showed 10.33-fold lower IC50 values for A2780 cells and 3.93-fold lower for OVCAR3 cells compared to non-targeted nanoparticles and demonstrated more cytotoxicity against ovarian cancer cells. Moreover, magnetically and folate receptor-targeted doxorubicin delivery system was significantly more effective for therapy of xenografted nude mice than free doxorubicin based on tumor shrinkages and biochemical parameters. In conclusion, it can be suggested that folate ligand-attached and biomimetically designed magnetic drug delivery system have advantages and potential for targeted ovarian cancer therapy.

21. In vitro and in vivo evaluation of folate receptor-targeted a novel magnetic drug delivery system for ovarian cancer therapy

Author

Ak, Güliz, Yilmaz, Habibe, Güneş, Aybike, and Sanlier, Senay Hamarat

Subjects
3. Good health
Abstract

Doxorubicin is widely used anticancer drug; however, use of doxorubicin is limited. Under externally applied magnetic field, magnetic agents can help to transport drug directly to tumor. Folate receptor is overexpressed in ovarian carcinomas. In this study, we aimed to develop magnetically responsive and folate receptor-targeted biomimetic drug delivery system for ovarian cancer therapy. Doxorubicin-loaded and glucose/gluconic acid-coated magnetic nanoparticles were synthesized and erythrocyte membrane vesicles were used for coating of nanoparticles. Folate ligand was anchored to surface so as to target receptor. Hydrodynamic size of nanocarrier was found as 91.2 ± 20.8 nm. The results showed that delivery system has controlled drug release profile and biocompatible features. In folate-free medium, folate receptor-targeted nanocarrier showed 10.33-fold lower IC50 values for A2780 cells and 3.93-fold lower for OVCAR3 cells compared to non-targeted nanoparticles and demonstrated more cytotoxicity against ovarian cancer cells. Moreover, magnetically and folate receptor-targeted doxorubicin delivery system was significantly more effective for therapy of xenografted nude mice than free doxorubicin based on tumor shrinkages and biochemical parameters. In conclusion, it can be suggested that folate ligand-attached and biomimetically designed magnetic drug delivery system have advantages and potential for targeted ovarian cancer therapy.

22. Design and synthesis of new heterocyclic compounds containing 5-[(1 H -1,2,4-triazol-1-yl)methyl]-3 H -1,2,4-triazole-3-thione structure as potent hEGFR inhibitors.

Author

Kolcuoglu Y, Bekircan O, Fazli H, Sahin E, Ture A, Akdemir A, and Hamarat Sanlier S

Subjects
Triazoles pharmacology, Triazoles chemistry, ErbB Receptors, Structure-Activity Relationship, Molecular Structure, Molecular Docking Simulation, Thiones, Heterocyclic Compounds
Abstract

EGFR is one of the important mediators of the signaling cascade that determines key roles in various biological processes such as growth, differentiation, metabolism and apoptosis in the cell in response to external and internal stimuli. In recent years, it has been proven that although this enzyme activity is tightly regulated in normal cells, if the enzyme activity cannot be controlled, it can lead to malignancy. EGFR is also considered a prominent macromolecule in targeted cancer chemotherapy. For this purpose, a comprehensive modeling studies were conducted against EGFR protein and novel molecules containing 5-[(1 H -1,2,4-triazol-1-yl)methyl]-3 H -1,2,4-triazole-3-thione structure were suggested to be synthesized. Among the synthesized molecules, compounds 7c , 8c , 8f and 8g were determined to have significant IC 50 values. Compound 8g was found to have the IC 50 value closest to the very well-known EGFR inhibitor Gefitinib with its noncompetitive inhibition form. K i value of compound 8g was calculated as 0.00232 µM.Communicated by Ramaswamy H. Sarma.

Published
2023
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