Oxaliplatin-Loaded Chitosan Nanoparticles Decorated with Cetuximab Single-Chain Variable Fragment for Human Colorectal Cancer Treatment
Objective: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Engineeredbiomolecules can be used as a targeted tool to deliver drugs directly to tumors that reduce the adverse effects of conventionaltreatments. We aimed to prepare non-targeted oxaliplatin-loaded...
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| Format: | Article |
| Language: | English |
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Royan Institute (ACECR), Tehran
2024-09-01
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| Series: | Cell Journal |
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| Online Access: | https://www.celljournal.org/article_718311_75fe512d40213af54f76cbf55fb1b980.pdf |
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| author | Khadijeh Falahzadeh Fariba Esmaeili Leila Nematollahi Elham Bayat Mehdi Khoobi Mohammadali Mazloomi Masumeh Jalalvand Reza Faridi Majidi Babak Negahdari |
| author_facet | Khadijeh Falahzadeh Fariba Esmaeili Leila Nematollahi Elham Bayat Mehdi Khoobi Mohammadali Mazloomi Masumeh Jalalvand Reza Faridi Majidi Babak Negahdari |
| author_sort | Khadijeh Falahzadeh |
| collection | DOAJ |
| description | Objective: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Engineeredbiomolecules can be used as a targeted tool to deliver drugs directly to tumors that reduce the adverse effects of conventionaltreatments. We aimed to prepare non-targeted oxaliplatin-loaded chitosan nanoparticles (OXPT-CS NPs) and targetedOXPT-CS NPs decorated with cetuximab single-chain variable fragment (scFv) to send both NPs to epidermal growth factorreceptor (EGFR) overexpressing HCT 116 cells, a human colorectal carcinoma cell line, for comparing their cytotoxicity.Materials and Methods: In this experimental study, OXPT-CS NPs were synthesized using a fluid system. Encapsulationefficiency percentage (EE%) and oxaliplatin release rate were evaluated. Western blot and cell-based ELISA confirmed scFvproduction and its binding ability to EGFR, respectively. The Fourier transform infrared spectroscopy (FTIR) determinedthe conjugation of scFv to OXPT-CS NPs. The NPs were characterized, and their toxicity against the HCT 116 cells wasevaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) and flow cytometry assays.Results: The EE% of OXPT-CS NPs was 93%, and the average diameters were 75.85 ± 8.81 nm and 92.48 ± 9.51before and after scFv conjugation, respectively. The scFv was purified via affinity chromatography. The western blotmethod and cell-based ELISA revealed successful purification of scFv and its attachment to EGFR on HCT 116 cells.The FTIR analysis determined the interactions between the scFv and OXPT-CS NPs. According to MTT and flowcytometry results, the targeted delivery system significantly reduced HCT 116 cancer cell viability and increasedapoptosis induction up to 99.8%.Conclusion: The scFv-OXPT-CS NPs demonstrated an increased cytotoxic function due to the presence of scFv in itsformulation. This delivery system offers a promising method for delivering chemotherapy drugs to cancer cells. Moreresearch is needed on the best strategies for improving treatment efficacy by targeting cancer cells. |
| format | Article |
| id | doaj-art-d55211db90cb41b387565d55b5d6dfe9 |
| institution | Kabale University |
| issn | 2228-5806 2228-5814 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Royan Institute (ACECR), Tehran |
| record_format | Article |
| series | Cell Journal |
| spelling | doaj-art-d55211db90cb41b387565d55b5d6dfe92025-01-19T09:34:57ZengRoyan Institute (ACECR), TehranCell Journal2228-58062228-58142024-09-0126953054210.22074/cellj.2024.2033893.1607718311Oxaliplatin-Loaded Chitosan Nanoparticles Decorated with Cetuximab Single-Chain Variable Fragment for Human Colorectal Cancer TreatmentKhadijeh Falahzadeh0Fariba Esmaeili1Leila Nematollahi2Elham Bayat3Mehdi Khoobi4Mohammadali Mazloomi5Masumeh Jalalvand6Reza Faridi Majidi7Babak Negahdari8Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, IranBiotechnology Research Center, Pasteur Institute of Iran, Tehran, IranBiotechnology Research Center, Pasteur Institute of Iran, Tehran, IranDepartment of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranDepartment of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, IranDepartment of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, IranObjective: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Engineeredbiomolecules can be used as a targeted tool to deliver drugs directly to tumors that reduce the adverse effects of conventionaltreatments. We aimed to prepare non-targeted oxaliplatin-loaded chitosan nanoparticles (OXPT-CS NPs) and targetedOXPT-CS NPs decorated with cetuximab single-chain variable fragment (scFv) to send both NPs to epidermal growth factorreceptor (EGFR) overexpressing HCT 116 cells, a human colorectal carcinoma cell line, for comparing their cytotoxicity.Materials and Methods: In this experimental study, OXPT-CS NPs were synthesized using a fluid system. Encapsulationefficiency percentage (EE%) and oxaliplatin release rate were evaluated. Western blot and cell-based ELISA confirmed scFvproduction and its binding ability to EGFR, respectively. The Fourier transform infrared spectroscopy (FTIR) determinedthe conjugation of scFv to OXPT-CS NPs. The NPs were characterized, and their toxicity against the HCT 116 cells wasevaluated using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) and flow cytometry assays.Results: The EE% of OXPT-CS NPs was 93%, and the average diameters were 75.85 ± 8.81 nm and 92.48 ± 9.51before and after scFv conjugation, respectively. The scFv was purified via affinity chromatography. The western blotmethod and cell-based ELISA revealed successful purification of scFv and its attachment to EGFR on HCT 116 cells.The FTIR analysis determined the interactions between the scFv and OXPT-CS NPs. According to MTT and flowcytometry results, the targeted delivery system significantly reduced HCT 116 cancer cell viability and increasedapoptosis induction up to 99.8%.Conclusion: The scFv-OXPT-CS NPs demonstrated an increased cytotoxic function due to the presence of scFv in itsformulation. This delivery system offers a promising method for delivering chemotherapy drugs to cancer cells. Moreresearch is needed on the best strategies for improving treatment efficacy by targeting cancer cells.https://www.celljournal.org/article_718311_75fe512d40213af54f76cbf55fb1b980.pdfcetuximabchitosancolorectal cancerdrug delivery systemsoxaliplatin |
| spellingShingle | Khadijeh Falahzadeh Fariba Esmaeili Leila Nematollahi Elham Bayat Mehdi Khoobi Mohammadali Mazloomi Masumeh Jalalvand Reza Faridi Majidi Babak Negahdari Oxaliplatin-Loaded Chitosan Nanoparticles Decorated with Cetuximab Single-Chain Variable Fragment for Human Colorectal Cancer Treatment Cell Journal cetuximab chitosan colorectal cancer drug delivery systems oxaliplatin |
| title | Oxaliplatin-Loaded Chitosan Nanoparticles Decorated with Cetuximab Single-Chain Variable Fragment for Human Colorectal Cancer Treatment |
| title_full | Oxaliplatin-Loaded Chitosan Nanoparticles Decorated with Cetuximab Single-Chain Variable Fragment for Human Colorectal Cancer Treatment |
| title_fullStr | Oxaliplatin-Loaded Chitosan Nanoparticles Decorated with Cetuximab Single-Chain Variable Fragment for Human Colorectal Cancer Treatment |
| title_full_unstemmed | Oxaliplatin-Loaded Chitosan Nanoparticles Decorated with Cetuximab Single-Chain Variable Fragment for Human Colorectal Cancer Treatment |
| title_short | Oxaliplatin-Loaded Chitosan Nanoparticles Decorated with Cetuximab Single-Chain Variable Fragment for Human Colorectal Cancer Treatment |
| title_sort | oxaliplatin loaded chitosan nanoparticles decorated with cetuximab single chain variable fragment for human colorectal cancer treatment |
| topic | cetuximab chitosan colorectal cancer drug delivery systems oxaliplatin |
| url | https://www.celljournal.org/article_718311_75fe512d40213af54f76cbf55fb1b980.pdf |
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