Development of a graphene oxide-poly lactide nanocomposite as a Smart Drug Delivery System

Int J Biol Macromol. 2021 Feb 1:169:521-531. doi: 10.1016/j.ijbiomac.2020.12.084. Epub 2020 Dec 16.

Abstract

In this study, a nanoscale graphene oxide polymer composite drug delivery system was synthesized and investigated for possible oral delivery of doxorubicin. A doxorubicin-loaded nanocomposite composed of graphene oxide/poly(2-hydroxyethylmethacrylate)-g-poly(lactide)-b-polyethyleneglycol-b-poly(2-hydroxyethylmethacrylate)-g-poly(lactide) GO/(PHEMA-g-PLA)-b-PEG-b-(PHEMA-g-PLA) was synthesized via reversible addition fragmentation chain (RAFT) and ring open polymerization (ROP). The GO/(PHEMA-g-PLA)-b-PEG-b- (PHEMA-g-PLA) nanocomposites was characterized by scanning electron microscopy (FE-SEM), thermogravimetry (TG), ultraviolet-visible (UV-Vis) spectroscopy, and dynamic light scattering (DLS). Doxorubicin was successfully loaded into the nanocomposite with a small particle size of 51 nm and an encapsulation efficiency (EE) of 82% ±1.12%. The results showed that DOX was attached to the graphene surface via hydrophobic interactions and π-π stacking. DOX release took place under neutral and acidic conditions, reaching 24.7% and 41.2% respectively after 72 h. Cytotoxicity experiments on 4T1 murine breast cancer cells demonstrated the antitumor activity of the DOX@GO nanocomposite. Biocompatibility, cell uptake, DAPI staining, Annexin V/PI double staining, intracellular reactive oxygen species (ROS) assay, and scratch healing assay were measured. The DOX@graphene nanocomposite system could be promising for breast cancer therapy.

Keywords: Chemotherapy; Doxorubicin; Drug delivery system; Graphene nanocomposite; Triple-negative breast cancer.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Dioxanes
  • Doxorubicin / administration & dosage
  • Doxorubicin / chemistry
  • Doxorubicin / pharmacology
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods*
  • Graphite / chemistry*
  • Humans
  • Lactates
  • Methacrylates
  • Mice
  • Nanocomposites / chemistry
  • Polyesters / chemistry*
  • Polyethylene Glycols
  • Polymers / chemistry
  • Polymethacrylic Acids

Substances

  • Dioxanes
  • Drug Carriers
  • Lactates
  • Methacrylates
  • Polyesters
  • Polymers
  • Polymethacrylic Acids
  • graphene oxide
  • poly(lactic acid)-block-poly(2-hydroxyethyl methacrylate)
  • poly(lactic acid-ethylene glycol)
  • Polyethylene Glycols
  • poly(lactide)
  • poly(ethyleneglycol-lactide)
  • hydroxyethyl methacrylate
  • Graphite
  • Doxorubicin
  • dilactide