Folic acid-appended galactoxyloglucan-capped iron oxide nanoparticles as a biocompatible nanotheranostic agent for tumor-targeted delivery of doxorubicin
| Autor: | R. Shiji, B. S. Unnikrishnan, K.S. Anusree, T. T. Sreelekha, Anitha Sen, G.U. Preethi, Manu M. Joseph, S. Maya |
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| Rok vydání: | 2020 |
| Předmět: |
Biodistribution
Cell Survival Antineoplastic Agents Apoptosis 02 engineering and technology Pharmacology Biochemistry Polyethylene Glycols 03 medical and health sciences chemistry.chemical_compound Mice Drug Delivery Systems Folic Acid Structural Biology Tandem Mass Spectrometry Cell Line Tumor medicine Animals Humans Doxorubicin Tissue Distribution Particle Size Cytotoxicity Magnetite Nanoparticles Molecular Biology Glucans 030304 developmental biology 0303 health sciences Galactose General Medicine 021001 nanoscience & nanotechnology Controlled release chemistry Folate receptor Toxicity Drug delivery Female Magnetic Iron Oxide Nanoparticles 0210 nano-technology Iron oxide nanoparticles medicine.drug Chromatography Liquid |
| Zdroj: | International journal of biological macromolecules. 168 |
| ISSN: | 1879-0003 |
| Popis: | Iron oxide nanoparticles (IONPs) are employed as MRI contrast agents and as effective drug delivery vehicles. However, the limited solubility and biodegradability of these nanoparticles need to be improved for safer biomedical applications. In an attempt to improve the bottlenecks associated with IONPs, the current study focuses on the synthesis of folic acid conjugated, galactoxyloglucan-iron oxide nanoparticles (FAPIONPs), for the loading and controlled release of the encapsulated chemotherapeutic agent doxorubicin (DOX). The as-designed DOX@FAPIONPs induced a dose-dependent increase in cytotoxicity in folate receptor-positive cells through a caspase-mediated programmed cell death pathway while bare DOX demonstrated a non-targeted toxicity profile. Using LC-MS/MS analysis, several major biological processes altered in treated cells, from which, cell cycle, cellular function and maintenance were the most affected. Detailed toxicity studies in healthy mice indicated the absence of any major side effects while bare drugs created substantial organ pathology. Gadolinium-based contrast agents have a risk of adverse effects, including nephrogenic systemic fibrosis overcome by the administration of DOX@FAPIONPs in xenograft mice model. Tumor-targeted biodistribution pattern with a favorable DOX pharmacokinetics will be the driving factor behind the appealing tumor reduction capacity and increased survival benefits demonstrated on solid tumor-bearing mice. |
| Databáze: | OpenAIRE |
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