Dual-targeting CD44 and mucin by hyaluronic acid and 5TR1 aptamer for epirubicin delivery into cancer cells: Synthesis, characterization, in vitro and in vivo evaluation
One of the revolutionized cancer treatment is active targeting nanomedicines. This study aims to create a dual-targeted drug delivery system for Epirubicin (EPI) to cancer cells. Hyaluronic acid (HA) is the first targeting ligand, and 5TR1 aptamer (5TR1) is the second targeting ligand to guide the d...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024008648 |
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| author | Zahra Jamshidi Reza Dehghan Mojgan Nejabat Khalil Abnous Seyed Mohammad Taghdisi Farzin Hadizadeh |
| author_facet | Zahra Jamshidi Reza Dehghan Mojgan Nejabat Khalil Abnous Seyed Mohammad Taghdisi Farzin Hadizadeh |
| author_sort | Zahra Jamshidi |
| collection | DOAJ |
| description | One of the revolutionized cancer treatment is active targeting nanomedicines. This study aims to create a dual-targeted drug delivery system for Epirubicin (EPI) to cancer cells. Hyaluronic acid (HA) is the first targeting ligand, and 5TR1 aptamer (5TR1) is the second targeting ligand to guide the dual-targeted drug delivery system to the cancer cells. HA is bound to highly expressed receptors like CD44 on cancer cells. 5TR1, DNA aptamer, is capable of recognizing MUC1 glycoprotein, which is overexpressed in cancer cells.The process involved binding EPI and 5TR1 to HA using adipic acid dihydrazide (AA) as a linker. The bond between the components was confirmed using 1H NMR. The binding of 5TR1 to HA-AA-EPI was confirmed using gel electrophoresis. The particle size (132.6 ± 9 nm) and Zeta Potential (−29 ± 4.4 mV) were measured for the final nanoformulation (HA-AA-EPI-5TR1). The release of EPI from the HA-AA-EPI-5TR1 nanoformulation was also studied at different pH levels. In the acidic pH (5.4 and 6.5) release pattern of EPI from the HA-AA-EPI-5TR1 nanoformulation was higher than physiological pH (7.4). The cytotoxicity and cellular uptake of the synthetic nanoformula were evaluated using MTT and flow cytometry analysis. Flow cytometry and cellular cytotoxicity studies were exhibited in a negative MUC1−cell line (CHO) and two positive MUC1+cell lines (MCF-7 and C26). Results confirmed that there is a notable contrast between the dual-targeted (HA-AA-EPI-5TR1) and single-targeted (HA-AA-EPI) nanoformulation in MCF-7 and C26 cell lines (MUC1+). In vivo studies showed that HA-AA-EPI-5TR1 nanoformulation has improved efficiency with limited side effect in C26 tumor-bearing mice. Also, Fluorescence imaging and pathological evaluation showed reduced side effects in the heart tissue of mice receiving HA-AA-EPI-5TR1 than free EPI.So, this targeted approach effectively delivers EPI to cancer cells with reduced side effects. |
| first_indexed | 2024-03-08T06:54:05Z |
| format | Article |
| id | doaj.art-760038c7ed624caeb8012c8a7306f2fd |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-08T06:54:05Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-760038c7ed624caeb8012c8a7306f2fd2024-02-03T06:38:34ZengElsevierHeliyon2405-84402024-01-01102e24833Dual-targeting CD44 and mucin by hyaluronic acid and 5TR1 aptamer for epirubicin delivery into cancer cells: Synthesis, characterization, in vitro and in vivo evaluationZahra Jamshidi0Reza Dehghan1Mojgan Nejabat2Khalil Abnous3Seyed Mohammad Taghdisi4Farzin Hadizadeh5Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Corresponding author.Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, IranTargeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranBiotechnology Research Institute, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Corresponding author. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.One of the revolutionized cancer treatment is active targeting nanomedicines. This study aims to create a dual-targeted drug delivery system for Epirubicin (EPI) to cancer cells. Hyaluronic acid (HA) is the first targeting ligand, and 5TR1 aptamer (5TR1) is the second targeting ligand to guide the dual-targeted drug delivery system to the cancer cells. HA is bound to highly expressed receptors like CD44 on cancer cells. 5TR1, DNA aptamer, is capable of recognizing MUC1 glycoprotein, which is overexpressed in cancer cells.The process involved binding EPI and 5TR1 to HA using adipic acid dihydrazide (AA) as a linker. The bond between the components was confirmed using 1H NMR. The binding of 5TR1 to HA-AA-EPI was confirmed using gel electrophoresis. The particle size (132.6 ± 9 nm) and Zeta Potential (−29 ± 4.4 mV) were measured for the final nanoformulation (HA-AA-EPI-5TR1). The release of EPI from the HA-AA-EPI-5TR1 nanoformulation was also studied at different pH levels. In the acidic pH (5.4 and 6.5) release pattern of EPI from the HA-AA-EPI-5TR1 nanoformulation was higher than physiological pH (7.4). The cytotoxicity and cellular uptake of the synthetic nanoformula were evaluated using MTT and flow cytometry analysis. Flow cytometry and cellular cytotoxicity studies were exhibited in a negative MUC1−cell line (CHO) and two positive MUC1+cell lines (MCF-7 and C26). Results confirmed that there is a notable contrast between the dual-targeted (HA-AA-EPI-5TR1) and single-targeted (HA-AA-EPI) nanoformulation in MCF-7 and C26 cell lines (MUC1+). In vivo studies showed that HA-AA-EPI-5TR1 nanoformulation has improved efficiency with limited side effect in C26 tumor-bearing mice. Also, Fluorescence imaging and pathological evaluation showed reduced side effects in the heart tissue of mice receiving HA-AA-EPI-5TR1 than free EPI.So, this targeted approach effectively delivers EPI to cancer cells with reduced side effects.http://www.sciencedirect.com/science/article/pii/S2405844024008648Breast cancerEpirubicinHyaluronic acidMUC15TR1 aptamerTargeted drug delivery |
| spellingShingle | Zahra Jamshidi Reza Dehghan Mojgan Nejabat Khalil Abnous Seyed Mohammad Taghdisi Farzin Hadizadeh Dual-targeting CD44 and mucin by hyaluronic acid and 5TR1 aptamer for epirubicin delivery into cancer cells: Synthesis, characterization, in vitro and in vivo evaluation Heliyon Breast cancer Epirubicin Hyaluronic acid MUC1 5TR1 aptamer Targeted drug delivery |
| title | Dual-targeting CD44 and mucin by hyaluronic acid and 5TR1 aptamer for epirubicin delivery into cancer cells: Synthesis, characterization, in vitro and in vivo evaluation |
| title_full | Dual-targeting CD44 and mucin by hyaluronic acid and 5TR1 aptamer for epirubicin delivery into cancer cells: Synthesis, characterization, in vitro and in vivo evaluation |
| title_fullStr | Dual-targeting CD44 and mucin by hyaluronic acid and 5TR1 aptamer for epirubicin delivery into cancer cells: Synthesis, characterization, in vitro and in vivo evaluation |
| title_full_unstemmed | Dual-targeting CD44 and mucin by hyaluronic acid and 5TR1 aptamer for epirubicin delivery into cancer cells: Synthesis, characterization, in vitro and in vivo evaluation |
| title_short | Dual-targeting CD44 and mucin by hyaluronic acid and 5TR1 aptamer for epirubicin delivery into cancer cells: Synthesis, characterization, in vitro and in vivo evaluation |
| title_sort | dual targeting cd44 and mucin by hyaluronic acid and 5tr1 aptamer for epirubicin delivery into cancer cells synthesis characterization in vitro and in vivo evaluation |
| topic | Breast cancer Epirubicin Hyaluronic acid MUC1 5TR1 aptamer Targeted drug delivery |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024008648 |
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