Dataset Information

Stimuli-Responsive Drug Delivery of Doxorubicin Using Magnetic Nanoparticle Conjugated Poly(ethylene glycol)-g-Chitosan Copolymer.

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.

SUBMITTER: Yoon HM

PROVIDER: S-EPMC8658650 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Stimuli-responsive biomaterials are used to facilitate drug and gene delivery by shielding the drug/gene during circulation times and selectively releasing the cargo at the desired target. Within stimuli-responsive materials, pH-responsive materials are exploited for delivery to specific organs, intracellular compartments, cancer cells, site of inflammation or infection as those sites are characterized by pH that is different from the blood pH. In this paper we use molecular dynamics (MD) simulations to design such pH-responsive biomaterials where the balance between the various intermolecular interactions (e.g., electrostatics, van der Waals) within the biomaterials allow biofunctional molecules to be reversibly shielded and exposed to the environment with change in pH. In our model the shielding aspect is imparted by a polyethylene glycol (PEG) brush and the pH-responsive component is a PEG-tethered oligopeptide that undergoes changes in conformations via protonation of residues upon changes in pH. Starting with a PEG-tethered peptide in a monodisperse short PEG brush, we first vary the composition and sequence of histidine (H), lysine (K), and glutamate (E) along the oligopeptide sequence to find the design parameters that maximize the shielding and exposure of the oligopeptide at pH ? 7.0 and pH < 7.0, respectively. Then, we probe the effect of the PEG brush on the conformations of the oligopeptides by simulating PEG-tethered peptide in a bimodal PEG brush containing short PEG and long PEG chains. We characterize the intermolecular interactions involving the PEG, peptide, and solvent that influence the shielded and exposed conformations of the oligopeptides at the two different pHs. In a short monodisperse PEG brush, with a longer PEG-tethered peptide containing large blocks of histidines that undergo change in protonation state as a response to pH change, placed between a protonated lysine and deprotonated glutamate, the PEG brush exhibits maximum shielding and exposure with pH change. This change from shielded to exposed state is driven by electrostatic repulsion upon H protonation. The presence of long PEG chains in a bimodal PEG brush leads to dominating PEG-peptide attractive interactions that reduces the contrast in shielded and exposed conformations of the PEG-tethered peptide upon protonation of histidines.

Dataset Information

Stimuli-Responsive Drug Delivery of Doxorubicin Using Magnetic Nanoparticle Conjugated Poly(ethylene glycol)-g-Chitosan Copolymer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets