Application of paramagnetic graphene quantum dots as a platform for simultaneous dual-modality bioimaging and tumor-targeted drug delivery

Chun Lin Huang, Chih Ching Huang, Fu-Der Mai, Chia Liang Yen, Shin Hwa Tzing, Hsiao Ting Hsieh, Yong Chien Ling, Jia Yaw Chang

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Here, we report the development of a multifunctional nanocarrier consisting of paramagnetic graphene quantum dots (GQDs), folate, and doxorubicin (Dox), used as delivery vehicles, a targeting ligand, and a chemotherapeutic drug, respectively. The paramagnetic GQDs, named folate-GdGQDs, were successfully prepared by covalently conjugating diethylenetriaminepentaacetic acid gadolinium and folic acid onto the surface of GQDs. The resultant folate-GdGQDs, which showed a longitudinal relaxivity r1 of 11.49 mM-1 s-1, greatly enhanced the brightness of the T1-weighted magnetic resonance (MR) images, indicating their potential for use as positive contrast agents for MR imaging (MRI). The feasibility of utilizing the folate-GdGQDs with strong luminescence emissions for targeted imaging of HeLa cells was also evaluated. An in vitro cell (HeLa and HepG2 cells) viability assay and in vivo evaluation of toxicity to the embryonic development of zebrafish showed that these folate-GdGQDs exhibited negligible cytotoxicity and excellent biocompatibility within the given range of concentrations. More importantly, strong therapeutic activity was achieved by loading Dox onto the surfaces of folate-GdGQDs through π-π stacking and hydrophobic interactions, leading to the formation of folate-GdGQD/Dox multifunctional nanocarriers. Approximately 80% of the loaded Dox was released from the folate-GdGQD/Dox nanocarriers under mild acidic conditions (pH 5.0), whereas only 20% of Dox was released at pH 7.0 after 48 h. Furthermore, these multifunctional nanocarriers could efficiently induce an inhibitory effect on HeLa cells, as confirmed by an in vitro cytotoxicity assay. The combined flow cytometry analysis and confocal laser scanning microscopic observation showed that these nanocarriers were efficiently taken up by the cancer cells overexpressing folate receptors. Taken together, these results suggested that the multifunctional nanocarriers could be used as promising targeted drug delivery vehicles for the diagnosis and image-guided chemotherapy of various cancers. This journal is

Original languageEnglish
Pages (from-to)651-664
Number of pages14
JournalJournal of Materials Chemistry B
Volume3
Issue number4
DOIs
Publication statusPublished - Jan 28 2015

Fingerprint

Quantum Dots
Graphite
Folic Acid
Graphene
Semiconductor quantum dots
Tumors
Magnetic resonance
Cytotoxicity
Assays
Doxorubicin
Pharmaceutical Preparations
Imaging techniques
Neoplasms
Chemotherapy
Acids
Flow cytometry
Gadolinium
Biocompatibility
HeLa Cells
Toxicity

ASJC Scopus subject areas

  • Biomedical Engineering
  • Medicine(all)
  • Chemistry(all)
  • Materials Science(all)

Cite this

Application of paramagnetic graphene quantum dots as a platform for simultaneous dual-modality bioimaging and tumor-targeted drug delivery. / Huang, Chun Lin; Huang, Chih Ching; Mai, Fu-Der; Yen, Chia Liang; Tzing, Shin Hwa; Hsieh, Hsiao Ting; Ling, Yong Chien; Chang, Jia Yaw.

In: Journal of Materials Chemistry B, Vol. 3, No. 4, 28.01.2015, p. 651-664.

Research output: Contribution to journalArticle

Huang, Chun Lin ; Huang, Chih Ching ; Mai, Fu-Der ; Yen, Chia Liang ; Tzing, Shin Hwa ; Hsieh, Hsiao Ting ; Ling, Yong Chien ; Chang, Jia Yaw. / Application of paramagnetic graphene quantum dots as a platform for simultaneous dual-modality bioimaging and tumor-targeted drug delivery. In: Journal of Materials Chemistry B. 2015 ; Vol. 3, No. 4. pp. 651-664.
@article{cc818cff7b074676851f8c33140b5e5d,
title = "Application of paramagnetic graphene quantum dots as a platform for simultaneous dual-modality bioimaging and tumor-targeted drug delivery",
abstract = "Here, we report the development of a multifunctional nanocarrier consisting of paramagnetic graphene quantum dots (GQDs), folate, and doxorubicin (Dox), used as delivery vehicles, a targeting ligand, and a chemotherapeutic drug, respectively. The paramagnetic GQDs, named folate-GdGQDs, were successfully prepared by covalently conjugating diethylenetriaminepentaacetic acid gadolinium and folic acid onto the surface of GQDs. The resultant folate-GdGQDs, which showed a longitudinal relaxivity r1 of 11.49 mM-1 s-1, greatly enhanced the brightness of the T1-weighted magnetic resonance (MR) images, indicating their potential for use as positive contrast agents for MR imaging (MRI). The feasibility of utilizing the folate-GdGQDs with strong luminescence emissions for targeted imaging of HeLa cells was also evaluated. An in vitro cell (HeLa and HepG2 cells) viability assay and in vivo evaluation of toxicity to the embryonic development of zebrafish showed that these folate-GdGQDs exhibited negligible cytotoxicity and excellent biocompatibility within the given range of concentrations. More importantly, strong therapeutic activity was achieved by loading Dox onto the surfaces of folate-GdGQDs through π-π stacking and hydrophobic interactions, leading to the formation of folate-GdGQD/Dox multifunctional nanocarriers. Approximately 80{\%} of the loaded Dox was released from the folate-GdGQD/Dox nanocarriers under mild acidic conditions (pH 5.0), whereas only 20{\%} of Dox was released at pH 7.0 after 48 h. Furthermore, these multifunctional nanocarriers could efficiently induce an inhibitory effect on HeLa cells, as confirmed by an in vitro cytotoxicity assay. The combined flow cytometry analysis and confocal laser scanning microscopic observation showed that these nanocarriers were efficiently taken up by the cancer cells overexpressing folate receptors. Taken together, these results suggested that the multifunctional nanocarriers could be used as promising targeted drug delivery vehicles for the diagnosis and image-guided chemotherapy of various cancers. This journal is",
author = "Huang, {Chun Lin} and Huang, {Chih Ching} and Fu-Der Mai and Yen, {Chia Liang} and Tzing, {Shin Hwa} and Hsieh, {Hsiao Ting} and Ling, {Yong Chien} and Chang, {Jia Yaw}",
year = "2015",
month = "1",
day = "28",
doi = "10.1039/c4tb01650e",
language = "English",
volume = "3",
pages = "651--664",
journal = "Journal of Materials Chemistry B",
issn = "2050-7518",
publisher = "Royal Society of Chemistry",
number = "4",

}

TY - JOUR

T1 - Application of paramagnetic graphene quantum dots as a platform for simultaneous dual-modality bioimaging and tumor-targeted drug delivery

AU - Huang, Chun Lin

AU - Huang, Chih Ching

AU - Mai, Fu-Der

AU - Yen, Chia Liang

AU - Tzing, Shin Hwa

AU - Hsieh, Hsiao Ting

AU - Ling, Yong Chien

AU - Chang, Jia Yaw

PY - 2015/1/28

Y1 - 2015/1/28

N2 - Here, we report the development of a multifunctional nanocarrier consisting of paramagnetic graphene quantum dots (GQDs), folate, and doxorubicin (Dox), used as delivery vehicles, a targeting ligand, and a chemotherapeutic drug, respectively. The paramagnetic GQDs, named folate-GdGQDs, were successfully prepared by covalently conjugating diethylenetriaminepentaacetic acid gadolinium and folic acid onto the surface of GQDs. The resultant folate-GdGQDs, which showed a longitudinal relaxivity r1 of 11.49 mM-1 s-1, greatly enhanced the brightness of the T1-weighted magnetic resonance (MR) images, indicating their potential for use as positive contrast agents for MR imaging (MRI). The feasibility of utilizing the folate-GdGQDs with strong luminescence emissions for targeted imaging of HeLa cells was also evaluated. An in vitro cell (HeLa and HepG2 cells) viability assay and in vivo evaluation of toxicity to the embryonic development of zebrafish showed that these folate-GdGQDs exhibited negligible cytotoxicity and excellent biocompatibility within the given range of concentrations. More importantly, strong therapeutic activity was achieved by loading Dox onto the surfaces of folate-GdGQDs through π-π stacking and hydrophobic interactions, leading to the formation of folate-GdGQD/Dox multifunctional nanocarriers. Approximately 80% of the loaded Dox was released from the folate-GdGQD/Dox nanocarriers under mild acidic conditions (pH 5.0), whereas only 20% of Dox was released at pH 7.0 after 48 h. Furthermore, these multifunctional nanocarriers could efficiently induce an inhibitory effect on HeLa cells, as confirmed by an in vitro cytotoxicity assay. The combined flow cytometry analysis and confocal laser scanning microscopic observation showed that these nanocarriers were efficiently taken up by the cancer cells overexpressing folate receptors. Taken together, these results suggested that the multifunctional nanocarriers could be used as promising targeted drug delivery vehicles for the diagnosis and image-guided chemotherapy of various cancers. This journal is

AB - Here, we report the development of a multifunctional nanocarrier consisting of paramagnetic graphene quantum dots (GQDs), folate, and doxorubicin (Dox), used as delivery vehicles, a targeting ligand, and a chemotherapeutic drug, respectively. The paramagnetic GQDs, named folate-GdGQDs, were successfully prepared by covalently conjugating diethylenetriaminepentaacetic acid gadolinium and folic acid onto the surface of GQDs. The resultant folate-GdGQDs, which showed a longitudinal relaxivity r1 of 11.49 mM-1 s-1, greatly enhanced the brightness of the T1-weighted magnetic resonance (MR) images, indicating their potential for use as positive contrast agents for MR imaging (MRI). The feasibility of utilizing the folate-GdGQDs with strong luminescence emissions for targeted imaging of HeLa cells was also evaluated. An in vitro cell (HeLa and HepG2 cells) viability assay and in vivo evaluation of toxicity to the embryonic development of zebrafish showed that these folate-GdGQDs exhibited negligible cytotoxicity and excellent biocompatibility within the given range of concentrations. More importantly, strong therapeutic activity was achieved by loading Dox onto the surfaces of folate-GdGQDs through π-π stacking and hydrophobic interactions, leading to the formation of folate-GdGQD/Dox multifunctional nanocarriers. Approximately 80% of the loaded Dox was released from the folate-GdGQD/Dox nanocarriers under mild acidic conditions (pH 5.0), whereas only 20% of Dox was released at pH 7.0 after 48 h. Furthermore, these multifunctional nanocarriers could efficiently induce an inhibitory effect on HeLa cells, as confirmed by an in vitro cytotoxicity assay. The combined flow cytometry analysis and confocal laser scanning microscopic observation showed that these nanocarriers were efficiently taken up by the cancer cells overexpressing folate receptors. Taken together, these results suggested that the multifunctional nanocarriers could be used as promising targeted drug delivery vehicles for the diagnosis and image-guided chemotherapy of various cancers. This journal is

UR - http://www.scopus.com/inward/record.url?scp=84919949229&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84919949229&partnerID=8YFLogxK

U2 - 10.1039/c4tb01650e

DO - 10.1039/c4tb01650e

M3 - Article

VL - 3

SP - 651

EP - 664

JO - Journal of Materials Chemistry B

JF - Journal of Materials Chemistry B

SN - 2050-7518

IS - 4

ER -