EGFR Targeted Cetuximab-Valine-Citrulline (vc)-Doxorubicin Immunoconjugates- Loaded Bovine Serum Albumin (BSA) Nanoparticles for Colorectal Tumor Therapy
| Autor: | Yanyan Liu, Yue Zhang, Jiasheng Tu, Yuanfen Liu, Yan Shen, Zixuan Ye |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Immunoconjugates
Proton Magnetic Resonance Spectroscopy Pharmaceutical Science Cetuximab 02 engineering and technology 01 natural sciences Mice Drug Delivery Systems International Journal of Nanomedicine Drug Discovery polycyclic compounds Tissue Distribution Bovine serum albumin Cytotoxicity Original Research biology medicine.diagnostic_test Chemistry Serum Albumin Bovine Valine General Medicine 021001 nanoscience & nanotechnology Endocytosis ErbB Receptors Drug delivery 0210 nano-technology Colorectal Neoplasms medicine.drug Antibody-drug conjugate Cell Survival Biophysics Bioengineering 010402 general chemistry doxorubicin Flow cytometry Biomaterials In vivo Cell Line Tumor bovine serum albumin medicine Animals Humans Doxorubicin MTT assay Particle Size colonic carcinoma Organic Chemistry technology industry and agriculture antibody–drug conjugate digestive system diseases 0104 chemical sciences carbohydrates (lipids) biology.protein Cancer research Citrulline Nanoparticles Cattle Adsorption epidermal growth factor receptor |
| Zdroj: | International Journal of Nanomedicine |
| ISSN: | 1178-2013 |
| Popis: | Zixuan Ye,1,* Yue Zhang,1,* Yuanfen Liu,2,* Yanyan Liu,1 Jiasheng Tu,1 Yan Shen1 1Department of Pharmaceutics, State Key Laboratory of Nature Medicines, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Jiangsu Health Vocational College, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Shen; Jiasheng TuDepartment of Pharmaceutics, State Key Laboratory of Nature Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, People’s Republic of ChinaTel +86 25 83271305Email shenyan@cpu.edu.cn; jiashengtu@aliyun.comBackground: Specific modifications to carriers to achieve targeted delivery of chemotherapeutics into malignant tissues are a critical point for efficient diagnosis and therapy. In this case, bovine serum albumin (BSA) was conjugated with cetuximab–valine–citrulline (vc)–doxorubicin (DOX) to target epidermal growth factor receptor (EGFR) and enable the release of drug in EGFR-overexpressed tumor cells.Methods: Maleimidocaproyl–valine–citrulline–p-aminobenzylcarbonyl-p-nitrophenol (MC-Val-Cit-PAB-PNP) and DOX were used to synthesize MC-Val-Cit-PAB-DOX, which was further linked with cetuximab to prepare antibody–drug conjugates (ADCs). Then, the ADCs were adsorbed to the surface of the BSA nanoparticles (NPs), which were prepared by a desolvation method to obtain cetuximab-vc-DOX-BSA-NPs. The cetuximab-vc-DOX conjugates adsorbed on the surface of the BSA nanoparticles were determined and optimized by size exclusion chromatography. An in vitro cytotoxicity study was conducted using a colon carcinoma cell line with different EGFR-expression levels to test the selectivity of cetuximab-vc-DOX-NPs.Results: The vc-DOX and cetuximab-vc-DOX conjugates were both synthesized successfully and their structural characteristics confirmed by 1H-NMR and SDS-PAGE. The MTT assay showed stronger cytotoxicity of cetuximab-vc-DOX-NPs versus control IgG-vc-DOX-NPs in EGFR–overexpressing RKO cells. Cellular binding and intracellular accumulation determined by flow cytometry and confocal laser scanning microscopy revealed the strong binding ability of cetuximab-vc-DOX-NPs to RKO cells. The in vivo imaging study demonstrated that cetuximab-vc-DOX-NPs exhibited higher fluorescent intensity in tumor tissues than non-decorated nanoparticles (IgG-vc-DOX-NPs). In vivo tumor inhibition and survival tests showed that cetuximab-vc-DOX-NPs revealed higher tumor inhibition efficacy and lower systemic toxicity than control IgG-vc-DOX- NPsConclusion: The obtained results emphasize that cetuximab-vc-DOX-NPs, with good tumor-targeting ability and low systemic toxicity, are a promising targeting system for drug delivery.Keywords: bovine serum albumin, antibody–drug conjugate, cetuximab, doxorubicin, colonic carcinoma, epidermal growth factor receptor |
| Databáze: | OpenAIRE |
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