Potential Advantages of Idarubicin-Loaded Trastuzumab-Coated Liposomes for Combating Head and Neck Squamous Cancer Cells
| Autor: | Marziyeh Ghanemi, Aminollah Pourshohod, Majid Zeinali, Ebrahim Barzegari, Akbar Akbari, Forouzan Absalan, Mostafa Jamalan |
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| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | Cell Journal, Vol 26, Iss 7, Pp 436-445 (2024) |
| Druh dokumentu: | article |
| ISSN: | 2228-5806 2228-5814 |
| DOI: | 10.22074/cellj.2024.2019704.1480 |
| Popis: | Objective: Head and neck squamous cell carcinoma (HNSCC) with a high mortality rate is among the most commontypes of cancer in the world. Human epidermal growth factor receptor 2 (HER2) is expressed higher than normal levelin the most HNSCC tumors, making them resistant to chemotherapy and radiotherapy. Therefore, HER2 has beenintroduced as a suitable target for anticancer drugs. The aim of this study is to examine the efficacy of a treatmentprotocol involving targeted delivery of idarubicin encapsulated in trastuzumab-decorated liposomes to HNSCC cells.Materials and Methods: In the current experimental study, efficacies of idarubicin, prepared liposomal idarubicin,and constructed immunoliposomal idarubicin (trastuzumab-decorated) were investigated in killing HN5 cells, a HER2-overexpressing HNSCC-originating cell line. Liposomal content of idarubicin and trastuzumab were qualified by UVVisiblespectroscopy and preparations were characterized for shape and size by atomic force microscopy (AFM) anddynamic light scattering (DLS). To clarify role of the missing parts of the available crystal structure (PDB ID: 1n8z)within trastuzumab-HER2 interactions, we used a 40 ns molecular dynamic simulation approach.Results: Based on the obtained results, liposomal idarubicin showed higher toxicity of the encapsulated drug on HN5cells compared to the traditional free drug formulations. The immunoliposomal form of idarubicin was more effectivethan the liposomal formulation, in killing of HN5 cells. In addition, simulation of interactions between trastuzumab andHER2 revealed that the missing parts (in the crystal structure) of HER2 have critical interaction with trastuzumab,through salt-bridges and hydrogen bonds.Conclusion: It seems that the prepared immunoliposomes could attach more efficiently to HER2 overexpressingcells, which consequently leads to increasing cellular uptake of idarubicin through a receptor-mediated endocytosismechanism. Moreover, simulation of the interaction between HER2 and trastuzumab suggested considerablepossibilities for increasing trastuzumab affinity to HER2. |
| Databáze: | Directory of Open Access Journals |
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