Folic acid-appended galactoxyloglucan-capped iron oxide nanoparticles as a biocompatible nanotheranostic agent for tumor-targeted delivery of doxorubicin

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 caspasemediated 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 andmaintenancewere themost affected. Detailed toxicity studies in healthy mice indicated the absence of anymajor side effectswhile 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. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

The study focused on synthesizing folic acid conjugated, galactoxyloglucan-iron oxide nanoparticles for drug loading and controlled release of chemotherapy drugs. The designed nanoparticles induced cytotoxicity in folate receptor-positive cells via a specific cell death pathway, while bare drugs demonstrated non-specific toxicity.