Lactoferrin-dual drug nanoconjugate: Synergistic anti-tumor efficacy of docetaxel and the NF-κB inhibitor celastrol
| Autor: | Amira Zaky, Kadria A. Elkhodairy, Sherine N. Khattab, Mohamed Teleb, Mahmoud M. Abd Elwakil, Mohammad A. Abdulkader, Fernando Albericio, Mona A. Abdelmoneem, Adnan A. Bekhit, Ahmed O. Elzoghby, Maged W. Helmy |
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| Rok vydání: | 2021 |
| Předmět: |
Drug
Materials science media_common.quotation_subject Antineoplastic Agents Bioengineering Docetaxel Nanoconjugates 02 engineering and technology 010402 general chemistry 01 natural sciences Biomaterials Mice chemistry.chemical_compound Drug Delivery Systems In vivo Cell Line Tumor medicine Animals Humans media_common Drug Carriers biology Lactoferrin NF-kappa B Cancer 021001 nanoscience & nanotechnology medicine.disease 0104 chemical sciences chemistry Mechanics of Materials Celastrol Cancer cell biology.protein Cancer research Nanoparticles Nanocarriers Pentacyclic Triterpenes 0210 nano-technology medicine.drug |
| Zdroj: | Materials Science and Engineering: C. 118:111422 |
| ISSN: | 0928-4931 |
| Popis: | Despite the progress in cancer nanotherapeutics, some obstacles still impede the success of nanocarriers and hinder their clinical translation. Low drug loading, premature drug release, off-target toxicity and multi-drug resistance are among the most difficult challenges. Lactoferrin (LF) has demonstrated a great tumor targeting capacity via its high binding affinity to low density lipoprotein (LDL) and transferrin (Tf) receptors overexpressed by various cancer cells. Herein, docetaxel (DTX) and celastrol (CST) could be successfully conjugated to LF backbone for synergistic breast cancer therapy. Most importantly, the conjugate self-assembled forming nanoparticles of 157.8 nm with elevated loading for both drugs (6.94 and 5.98% for DTX and CST, respectively) without risk of nanocarrier instability. Moreover, the nanoconjugate demonstrated enhanced in vivo anti-tumor efficacy in breast cancer-bearing mice, as reflected by a reduction in tumor volume, prolonged survival rate and significant suppression of NF-κB p65, TNF-α, COX-2 and Ki-67 expression levels compared to the group given free combined DTX/CST therapy and to positive control. This study demonstrated the proof-of-principle for dual drug coupling to LF as a versatile nanoplatform that could augment their synergistic anticancer efficacy. |
| Databáze: | OpenAIRE |
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