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
N1 - Publisher Copyright:
© The Royal Society of Chemistry 2015.
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
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U2 - 10.1039/c4tb01650e
DO - 10.1039/c4tb01650e
M3 - Article
AN - SCOPUS:84919949229
SN - 2050-7518
VL - 3
SP - 651
EP - 664
JO - Journal of Materials Chemistry B
JF - Journal of Materials Chemistry B
IS - 4
ER -
