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Preparation and tumor cell model based biobehavioral evaluation of the nanocarrier system using partially reduced graphene oxide functionalized by surfactant.

Wang Y, Liu K, Luo Z, Duan Y - Int J Nanomedicine (2015)

Bottom Line: The partially reduced graphene oxide sheets functionalized by surfactant exhibit good dispersibility.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.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.

View Article: PubMed Central - PubMed

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.

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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus

Microscopic morphology investigations of PSSG.Notes: (A) SEM image of the undulating surface of PSSG. (B) Paper-like, single-layer or partially folded rGO sheets. (C) AFM images with height profiles of GO; (D) and PSSG.Abbreviations: PSSG, PSS-decorated nanographene; PSS, poly(sodium 4-styrenesulfonate); SEM, scanning electron microscopy; TEM, transmission electron microscopy; AFM, atomic force microscopy; rGO, reduced graphene oxide.
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f2-ijn-10-4605: Microscopic morphology investigations of PSSG.Notes: (A) SEM image of the undulating surface of PSSG. (B) Paper-like, single-layer or partially folded rGO sheets. (C) AFM images with height profiles of GO; (D) and PSSG.Abbreviations: PSSG, PSS-decorated nanographene; PSS, poly(sodium 4-styrenesulfonate); SEM, scanning electron microscopy; TEM, transmission electron microscopy; AFM, atomic force microscopy; rGO, reduced graphene oxide.

Mentions: The sizes and morphological characteristics of PSSG were observed through SEM, TEM, and AFM. SEM imaging shows the undulating surface of PSSG (Figure 2A), which could provide a rough view of the nanomaterial. As a nanocarrier, the average size is important for systemic circulation. The TEM images in Figure 2B showed that the paper-like single-layer or partially folded rGO sheets appear transparent and that more than 90% of the PSSG sheets were smaller than 500 nm. Also, the exact size and thickness of GO and PSSG were compared with AFM images. Measurements in and Figure 2C and D illustrate that after reduction and ultrasonication, due to the π–π noncovalent interaction between PSS and rGO,31,34 the average thickness of PSSG changed from 1 to 1.8 nm, while the size reduced to less than 1 μm, which was accordant with the reported literatures.27,36


Preparation and tumor cell model based biobehavioral evaluation of the nanocarrier system using partially reduced graphene oxide functionalized by surfactant.

Wang Y, Liu K, Luo Z, Duan Y - Int J Nanomedicine (2015)

Microscopic morphology investigations of PSSG.Notes: (A) SEM image of the undulating surface of PSSG. (B) Paper-like, single-layer or partially folded rGO sheets. (C) AFM images with height profiles of GO; (D) and PSSG.Abbreviations: PSSG, PSS-decorated nanographene; PSS, poly(sodium 4-styrenesulfonate); SEM, scanning electron microscopy; TEM, transmission electron microscopy; AFM, atomic force microscopy; rGO, reduced graphene oxide.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4514384&req=5

f2-ijn-10-4605: Microscopic morphology investigations of PSSG.Notes: (A) SEM image of the undulating surface of PSSG. (B) Paper-like, single-layer or partially folded rGO sheets. (C) AFM images with height profiles of GO; (D) and PSSG.Abbreviations: PSSG, PSS-decorated nanographene; PSS, poly(sodium 4-styrenesulfonate); SEM, scanning electron microscopy; TEM, transmission electron microscopy; AFM, atomic force microscopy; rGO, reduced graphene oxide.
Mentions: The sizes and morphological characteristics of PSSG were observed through SEM, TEM, and AFM. SEM imaging shows the undulating surface of PSSG (Figure 2A), which could provide a rough view of the nanomaterial. As a nanocarrier, the average size is important for systemic circulation. The TEM images in Figure 2B showed that the paper-like single-layer or partially folded rGO sheets appear transparent and that more than 90% of the PSSG sheets were smaller than 500 nm. Also, the exact size and thickness of GO and PSSG were compared with AFM images. Measurements in and Figure 2C and D illustrate that after reduction and ultrasonication, due to the π–π noncovalent interaction between PSS and rGO,31,34 the average thickness of PSSG changed from 1 to 1.8 nm, while the size reduced to less than 1 μm, which was accordant with the reported literatures.27,36

Bottom Line: The partially reduced graphene oxide sheets functionalized by surfactant exhibit good dispersibility.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.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.

View Article: PubMed Central - PubMed

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.

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.

Conclusion: 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.

No MeSH data available.


Related in: MedlinePlus