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Published on: April 22, 2019
Potential Advantages of Idarubicin-Loaded Trastuzumab-Coated Liposomes for Combating Head and Neck Squamous Cancer
Marziyeh Ghanemi1, Aminollah Pourshohod2, Majid Zeinali3
1Department of Orthodontics, School of Dentistry, Shahed University, Tehran, Iran.
Objective:
Head and neck squamous cell carcinoma (HNSCC) with a high mortality rate is among the most common types of cancer in the world. Human epidermal growth factor receptor 2 (HER2) is expressed higher than normal level in the most HNSCC tumors, making them resistant to chemotherapy and radiotherapy. Therefore, HER2 has been introduced as a suitable target for anticancer drugs. The aim of this study is to examine the efficacy of a treatment protocol 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 UVVisible spectroscopy and preparations were characterized for shape and size by atomic force microscopy (AFM) and dynamic 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 HN5 cells compared to the traditional free drug formulations. The immunoliposomal form of idarubicin was more effective than the liposomal formulation, in killing of HN5 cells. In addition, simulation of interactions between trastuzumab and HER2 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 overexpressing cells, which consequently leads to increasing cellular uptake of idarubicin through a receptor-mediated endocytosis mechanism. Moreover, simulation of the interaction between HER2 and trastuzumab suggested considerable possibilities for increasing trastuzumab affinity to HER2.
Insights
Targeted liposomes carrying idarubicin demonstrated enhanced efficacy against HER2-positive head and neck squamous cell carcinoma (HNSCC) cells. Trastuzumab-decorated immunoliposomes improved drug delivery and cancer cell killing.
Area of Science:
- Oncology
- Nanomedicine
- Biochemistry
Background:
- Head and neck squamous cell carcinoma (HNSCC) presents a high mortality rate and resistance to conventional therapies.
- Human epidermal growth factor receptor 2 (HER2) overexpression in HNSCC contributes to treatment resistance, making it a viable therapeutic target.
- Targeted drug delivery systems offer a promising strategy to enhance anticancer efficacy and overcome resistance.
Purpose of the Study:
- To evaluate the efficacy of idarubicin delivered via trastuzumab-decorated liposomes for HNSCC treatment.
- To investigate the targeted delivery and cytotoxic effects of immunoliposomes on HER2-overexpressing HNSCC cells.
- To explore the molecular interactions between trastuzumab and HER2 to optimize therapeutic strategies.
Main Methods:
- Experimental evaluation of free idarubicin, liposomal idarubicin, and trastuzumab-decorated immunoliposomal idarubicin against HN5 HNSCC cells.
- Characterization of liposomal formulations using UV-Visible spectroscopy, atomic force microscopy (AFM), and dynamic light scattering (DLS).
- Molecular dynamics simulation to analyze trastuzumab-HER2 interactions and elucidate the role of specific binding sites.
Main Results:
- Liposomal idarubicin exhibited superior toxicity against HN5 cells compared to free idarubicin.
- Trastuzumab-decorated immunoliposomes demonstrated enhanced efficacy in killing HN5 cells over standard liposomes.
- Molecular dynamics simulations revealed critical interactions between trastuzumab and specific regions of HER2, including salt bridges and hydrogen bonds.
Conclusions:
- Trastuzumab-decorated immunoliposomes effectively target HER2-overexpressing HNSCC cells, enhancing idarubicin uptake via receptor-mediated endocytosis.
- The findings suggest that immunoliposomes are a promising platform for targeted HNSCC therapy.
- Further optimization of trastuzumab affinity to HER2 could lead to improved therapeutic outcomes.
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