A functionalized graphene oxide with improved cytocompatibility for stimuli-responsive co-delivery of curcumin and doxorubicin in cancer treatment

Sci Rep. 2022 Feb 4;12(1):1959. doi: 10.1038/s41598-022-05793-9.

Abstract

Nowadays, the usage of nanoparticles in various fields such as drug delivery, attracts the attention of many researchers in the treatment of cancers. Graphene oxide (GO) is one of the novel drug delivery systems which is used broadly owing to its unique features. In this survey, doxorubicin (DOX) was accompanied by natural medicine, curcumin (CUR), to diminish its side effects and enhance its efficiency. Cytotoxicity assay in human gastric cancer (AGS), prostate cancer (PC3), and ovarian cancer (A2780), was evaluated. Also, the uptake of DOX and CUR into cells, was assessed using a fluorescence microscope. Moreover, real-time PCR was applied for the evaluation of the expression of RB1 and CDK2 genes, which were involved in the cell cycle. In both separate and simultaneous forms, DOX and CUR were loaded with high efficiency and the release behavior of both drugs was pH-sensitive. The higher release rate was attained at pH 5.5 and 42 °C for DOX (80.23%) and CUR (13.06), respectively. The intensity of fluorescence in the free form of the drugs, was higher than the loaded form. In the same concentration, the free form of CUR and DOX were more toxic than the loaded form in all cell lines. Also, free drugs showed more impact on the expression of RB1 and CDK2 genes. Co-delivery of CUR and DOX into the mentioned cell lines, was more effective than the free form of CUR and DOX due to its lower toxicity to normal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / chemistry
  • Antineoplastic Combined Chemotherapy Protocols / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Curcumin / administration & dosage*
  • Curcumin / chemistry
  • Curcumin / metabolism
  • Cyclin-Dependent Kinase 2 / genetics
  • Cyclin-Dependent Kinase 2 / metabolism
  • Doxorubicin / administration & dosage*
  • Doxorubicin / chemistry
  • Doxorubicin / metabolism
  • Drug Carriers*
  • Drug Compounding
  • Drug Liberation
  • Female
  • Graphite / chemistry*
  • Humans
  • Hydrogen-Ion Concentration
  • Kinetics
  • Male
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Retinoblastoma Binding Proteins / genetics
  • Retinoblastoma Binding Proteins / metabolism
  • Stimuli Responsive Polymers*
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Drug Carriers
  • RB1 protein, human
  • Retinoblastoma Binding Proteins
  • Stimuli Responsive Polymers
  • graphene oxide
  • Graphite
  • Doxorubicin
  • Ubiquitin-Protein Ligases
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2
  • Curcumin