title: Preparation and tumor cell model based biobehavioral evaluation of the nanocarrier system using partially reduced graphene oxide functionalized by surfactant.
abstract: BACKGROUND
  Currently, surfactant-functionalized nanomaterials are tending toward development of novel tumor-targeted drug carriers to overcome multidrug resistance in cancer therapy. Now, investigating the biocompatibility and uptake mechanism of specific drug delivery systems is a growing trend, but usually a troublesome issue, in simple pharmaceutical research.
  
  
  METHODS
  We first reported the partially reduced graphene oxide modified with poly(sodium 4-styrenesulfonate) (PSS) as a nanocarrier system. Then, the nanocarrier was characterized by atomic force microscope, scanning electron microscope, high-resolution transmission electron microscope, ultraviolet-visible (UV-vis) spectroscopy, Fourier transform infrared spectroscopy, X-Ray powder diffraction, and Raman spectroscopy. Epirubicin (EPI) was attached to PSSG via π-π stacking, hydrogen bonding, and physical absorption to form conjugates of PSSG-EPI. The adsorption and desorption profiles, cytotoxicity coupled with drug accumulation, and uptake of PSSG and PSSG-EPI were evaluated. Finally, the subcellular behaviors, distribution, and biological fate of the drug delivery system were explored by confocal laser scanning microscope using direct fluorescence colocalization imaging and transmission electron microscopy.
  
  
  RESULTS
  The partially reduced graphene oxide sheets functionalized by surfactant exhibit good dispersibility. Moreover, due to much less carboxyl groups retained on the edge of PSSG sheets, the nanocarriers exhibit biocompatibility in vitro. The obtained PSSG shows a high drug-loading capacity of 2.22 mg/mg. The complexes of PSSG-EPI can be transferred to lysosomes in 2 hours through endocytosis, then the drug is released in the cytoplasm in 8 hours, and ultimately EPI is delivered into cell nucleus to exhibit medicinal effects in 1 day.
  
  
  CONCLUSIONS
  The comprehensive exploration of the biological uptake mechanism of functional graphene-mediated tumor cell targeting model provides a typical protocol for evaluation of drug delivery system and will benefit the discovery of new surfactant-modified nanocarriers in nanomedicine.
authors.affiliation: Research Center of Analytical Instrumentation, Key Laboratory of Bio-resource and Eco-environment, Ministry of Education, College of Life Science, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Research Center of Analytical Instrumentation, Key Laboratory of Bio-resource and Eco-environment, Ministry of Education, College of Life Science, Sichuan University, Chengdu, People's Republic of China ; Faculty of Biotechnology Industry, Chengdu University, Chengdu, People's Republic of China.
authors.forename: Kunping
authors.initials: K
authors.lastname: Liu
authors.affiliation: Research Center of Analytical Instrumentation, Key Laboratory of Bio-resource and Eco-environment, Ministry of Education, College of Life Science, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Zewei
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Research Center of Analytical Instrumentation, Key Laboratory of Bio-resource and Eco-environment, Ministry of Education, College of Life Science, Sichuan University, Chengdu, People's Republic of China.
authors.forename: Yixiang
authors.initials: Y
authors.lastname: Duan
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D050997:Nanomedicine; D049329:Nanostructures / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D013501:Surface-Active Agents; D006108:Graphite
keywords: biocompatibility; controlled release; cytotoxicity; drug delivery; epirubicin; fluorescence colocalization