Abstract
Stimuli-responsive nanoparticles are regarded as an ideal candidate for anticancer drug targeting. We synthesized glutathione (GSH) and magnetic-sensitive nanocomposites for a dual-targeting strategy. To achieve this goal, methoxy poly (ethylene glycol) (MePEG) was grafted to water-soluble chitosan (abbreviated as ChitoPEG). Then doxorubicin (DOX) was conjugated to the backbone of chitosan via disulfide linkage. Iron oxide (IO) magnetic nanoparticles were also conjugated to the backbone of chitosan to provide magnetic sensitivity. In morphological observation, images from a transmission electron microscope (TEM) showed that IO nanoparticles were embedded in the ChitoPEG/DOX/IO nanocomposites. In a drug release study, GSH addition accelerated DOX release rate from nanocomposites, indicating that nanocomposites have redox-responsiveness. Furthermore, external magnetic stimulus concentrated nanocomposites in the magnetic field and then provided efficient internalization of nanocomposites into cancer cells in cell culture experiments. In an animal study with CT26 cell-bearing mice, nanocomposites showed superior magnetic sensitivity and then preferentially targeted tumor tissues in the field of external magnetic stimulus. Nanocomposites composed of ChitoPEG/DOX/IO nanoparticle conjugates have excellent anticancer drug targeting properties.
Highlights
Colloidal-based drug delivery vehicles such as core-shell-type nanoparticles, polymeric micelles, and nano-conjugates have been extensively investigated to achieve sitespecific drug delivery for the treatment of diseased cells or organs [1,2,3,4,5]
Introduction of PEG in the backbone of the Water-soluble chitosan (WSC) chain may provide stealth properties to nanoparticles; i.e., hydrophilic PEG domain normally forms the outer shell of the nanoparticles and protects nanoparticles from the attack of the reticuloendothelial system (RES) [1,2]
The peaks between 4.4 and 4.6 ppm were estimated to be due to H-1 hydrogen of chitosan and 11–15 hydrogens of doxorubicin
Summary
Colloidal-based drug delivery vehicles such as core-shell-type nanoparticles, polymeric micelles, and nano-conjugates have been extensively investigated to achieve sitespecific drug delivery for the treatment of diseased cells or organs [1,2,3,4,5]. Due to their small diameter, nanoparticles can be administered intravenously and delivered to specific organs, tissues, or cells [3,4,5]. Guo et al reported that an external magnetic field enhances cellular internalization and tumor accumulation of IO nanoparticles [12] They argued that the tumor-targeting efficiency of IO nanoparticles was varied according to the diameter [12]. Other researchers reported the synthesis of Fe3O4-decorated Cu9S5@-mSiO2@Fe3O4PEG nanocomposites and external magnetic stimulus induces synergistic therapeutic effect against H22 tumor-bearing animal study [13]
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