Gadolinium-functionalized nanographene oxide for combined drug and microRNA delivery and magnetic resonance imaging

Hung Wei Yang; Chiung Yin Huang; Chih Wen Lin; Hao Li Liu; Chia Wen Huang; Shih Sheng Liao; Pin Yuan Chen; Yu Jen Lu; Kuo Chen Wei; Chen Chi M. Ma

doi:10.1016/j.biomaterials.2014.04.057

Gadolinium-functionalized nanographene oxide for combined drug and microRNA delivery and magnetic resonance imaging

Hung Wei Yang, Chiung Yin Huang, Chih Wen Lin, Hao Li Liu, Chia Wen Huang, Shih Sheng Liao, Pin Yuan Chen, Yu Jen Lu, Kuo Chen Wei, Chen Chi M. Ma

Department of Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

146 Citations (Scopus)

Abstract

The delivery of anti-cancer therapeutics to tumors at clinically effective concentrations, while avoiding nonspecific toxicity, remains a major challenge for cancer treatment. Here we present nanoparticles of poly(amidoamine) dendrimer-grafted gadolinium-functionalized nanographene oxide (Gd-NGO) as effective carriers to deliver both chemotherapeutic drugs and highly specific gene-targeting agents such as microRNAs (miRNAs) to cancer cells. The positively charged surface of Gd-NGO was capable of simultaneous adsorption of the anti-cancer drug epirubicin (EPI) and interaction with negatively charged Let-7g miRNA. Using human glioblastoma (U87) cells as a model, we found that this conjugate of Let-7g and EPI (Gd-NGO/Let-7g/EPI) not only exhibited considerably higher transfection efficiency, but also induced better inhibition of cancer cell growth than Gd-NGO/Let-7g or Gd-NGO/EPI. The concentration of Gd-NGO/Let-7g/EPI required for 50% inhibition of cellular growth (IC50) was significantly reduced (to the equivalent of 1.3μg/mL EPI) compared to Gd-NGO/EPI (3.4μg/mL EPI). In addition, Gd-NGO/Let-7g/EPI could be used as a contrast agent for magnetic resonance imaging to identify the location and extent of blood-brain barrier opening and quantitate drug delivery to tumor tissues. These results suggest that Gd-NGO/Let-7g/EPI may be a promising non-viral vector for chemogene therapy and molecular imaging diagnosis in future clinical applications.

Original language	English
Pages (from-to)	6534-6542
Number of pages	9
Journal	Biomaterials
Volume	35
Issue number	24
DOIs	https://doi.org/10.1016/j.biomaterials.2014.04.057
Publication status	Published - 2014 Aug

All Science Journal Classification (ASJC) codes

Biophysics
Bioengineering
Ceramics and Composites
Biomaterials
Mechanics of Materials

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10.1016/j.biomaterials.2014.04.057

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@article{540c3a9785d043ab86f7c2d5bd8be341,

title = "Gadolinium-functionalized nanographene oxide for combined drug and microRNA delivery and magnetic resonance imaging",

abstract = "The delivery of anti-cancer therapeutics to tumors at clinically effective concentrations, while avoiding nonspecific toxicity, remains a major challenge for cancer treatment. Here we present nanoparticles of poly(amidoamine) dendrimer-grafted gadolinium-functionalized nanographene oxide (Gd-NGO) as effective carriers to deliver both chemotherapeutic drugs and highly specific gene-targeting agents such as microRNAs (miRNAs) to cancer cells. The positively charged surface of Gd-NGO was capable of simultaneous adsorption of the anti-cancer drug epirubicin (EPI) and interaction with negatively charged Let-7g miRNA. Using human glioblastoma (U87) cells as a model, we found that this conjugate of Let-7g and EPI (Gd-NGO/Let-7g/EPI) not only exhibited considerably higher transfection efficiency, but also induced better inhibition of cancer cell growth than Gd-NGO/Let-7g or Gd-NGO/EPI. The concentration of Gd-NGO/Let-7g/EPI required for 50% inhibition of cellular growth (IC50) was significantly reduced (to the equivalent of 1.3μg/mL EPI) compared to Gd-NGO/EPI (3.4μg/mL EPI). In addition, Gd-NGO/Let-7g/EPI could be used as a contrast agent for magnetic resonance imaging to identify the location and extent of blood-brain barrier opening and quantitate drug delivery to tumor tissues. These results suggest that Gd-NGO/Let-7g/EPI may be a promising non-viral vector for chemogene therapy and molecular imaging diagnosis in future clinical applications.",

author = "Yang, {Hung Wei} and Huang, {Chiung Yin} and Lin, {Chih Wen} and Liu, {Hao Li} and Huang, {Chia Wen} and Liao, {Shih Sheng} and Chen, {Pin Yuan} and Lu, {Yu Jen} and Wei, {Kuo Chen} and Ma, {Chen Chi M.}",

note = "Funding Information: We thank the National Science Council of the Republic of China , National Health Research Institutes of Taiwan , Chang Gung Memorial Hospital , Industrial Technology Research Institute ( 103A0045J2 ), and National Tsing Hua University ( 103N2753E1 ) for financial support ( NSC 102-2221-E-007-003-(102) , NSC 102-2622-E-007-024-CC3 , NSC 102-2314-B-182A-068-MY3 , NSC 102-2120-M-182A-002-CC1 , NHRI-EX103-10004NI , CMRPG3D0571, CMRPG3B1012, CMRPG392103, CORPG3C0041, CMRPG390071, CMRPG380571, 103A0045J2, 103N2753E1). The authors thank the Boost Program from Low Carbon Energy Research Center of National Tsing Hua University; Chang Gung Memorial Hospital Animal Molecular Imaging Center for assistance with 7T-MRI and Microscopy Core Laboratory.",

year = "2014",

month = aug,

doi = "10.1016/j.biomaterials.2014.04.057",

language = "English",

volume = "35",

pages = "6534--6542",

journal = "Biomaterials",

issn = "0142-9612",

publisher = "Elsevier BV",

number = "24",

}

TY - JOUR

T1 - Gadolinium-functionalized nanographene oxide for combined drug and microRNA delivery and magnetic resonance imaging

AU - Yang, Hung Wei

AU - Huang, Chiung Yin

AU - Lin, Chih Wen

AU - Liu, Hao Li

AU - Huang, Chia Wen

AU - Liao, Shih Sheng

AU - Chen, Pin Yuan

AU - Lu, Yu Jen

AU - Wei, Kuo Chen

AU - Ma, Chen Chi M.

N1 - Funding Information: We thank the National Science Council of the Republic of China , National Health Research Institutes of Taiwan , Chang Gung Memorial Hospital , Industrial Technology Research Institute ( 103A0045J2 ), and National Tsing Hua University ( 103N2753E1 ) for financial support ( NSC 102-2221-E-007-003-(102) , NSC 102-2622-E-007-024-CC3 , NSC 102-2314-B-182A-068-MY3 , NSC 102-2120-M-182A-002-CC1 , NHRI-EX103-10004NI , CMRPG3D0571, CMRPG3B1012, CMRPG392103, CORPG3C0041, CMRPG390071, CMRPG380571, 103A0045J2, 103N2753E1). The authors thank the Boost Program from Low Carbon Energy Research Center of National Tsing Hua University; Chang Gung Memorial Hospital Animal Molecular Imaging Center for assistance with 7T-MRI and Microscopy Core Laboratory.

PY - 2014/8

Y1 - 2014/8

N2 - The delivery of anti-cancer therapeutics to tumors at clinically effective concentrations, while avoiding nonspecific toxicity, remains a major challenge for cancer treatment. Here we present nanoparticles of poly(amidoamine) dendrimer-grafted gadolinium-functionalized nanographene oxide (Gd-NGO) as effective carriers to deliver both chemotherapeutic drugs and highly specific gene-targeting agents such as microRNAs (miRNAs) to cancer cells. The positively charged surface of Gd-NGO was capable of simultaneous adsorption of the anti-cancer drug epirubicin (EPI) and interaction with negatively charged Let-7g miRNA. Using human glioblastoma (U87) cells as a model, we found that this conjugate of Let-7g and EPI (Gd-NGO/Let-7g/EPI) not only exhibited considerably higher transfection efficiency, but also induced better inhibition of cancer cell growth than Gd-NGO/Let-7g or Gd-NGO/EPI. The concentration of Gd-NGO/Let-7g/EPI required for 50% inhibition of cellular growth (IC50) was significantly reduced (to the equivalent of 1.3μg/mL EPI) compared to Gd-NGO/EPI (3.4μg/mL EPI). In addition, Gd-NGO/Let-7g/EPI could be used as a contrast agent for magnetic resonance imaging to identify the location and extent of blood-brain barrier opening and quantitate drug delivery to tumor tissues. These results suggest that Gd-NGO/Let-7g/EPI may be a promising non-viral vector for chemogene therapy and molecular imaging diagnosis in future clinical applications.

AB - The delivery of anti-cancer therapeutics to tumors at clinically effective concentrations, while avoiding nonspecific toxicity, remains a major challenge for cancer treatment. Here we present nanoparticles of poly(amidoamine) dendrimer-grafted gadolinium-functionalized nanographene oxide (Gd-NGO) as effective carriers to deliver both chemotherapeutic drugs and highly specific gene-targeting agents such as microRNAs (miRNAs) to cancer cells. The positively charged surface of Gd-NGO was capable of simultaneous adsorption of the anti-cancer drug epirubicin (EPI) and interaction with negatively charged Let-7g miRNA. Using human glioblastoma (U87) cells as a model, we found that this conjugate of Let-7g and EPI (Gd-NGO/Let-7g/EPI) not only exhibited considerably higher transfection efficiency, but also induced better inhibition of cancer cell growth than Gd-NGO/Let-7g or Gd-NGO/EPI. The concentration of Gd-NGO/Let-7g/EPI required for 50% inhibition of cellular growth (IC50) was significantly reduced (to the equivalent of 1.3μg/mL EPI) compared to Gd-NGO/EPI (3.4μg/mL EPI). In addition, Gd-NGO/Let-7g/EPI could be used as a contrast agent for magnetic resonance imaging to identify the location and extent of blood-brain barrier opening and quantitate drug delivery to tumor tissues. These results suggest that Gd-NGO/Let-7g/EPI may be a promising non-viral vector for chemogene therapy and molecular imaging diagnosis in future clinical applications.

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DO - 10.1016/j.biomaterials.2014.04.057

M3 - Article

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SN - 0142-9612

VL - 35

SP - 6534

EP - 6542

JO - Biomaterials

JF - Biomaterials

IS - 24

ER -

Gadolinium-functionalized nanographene oxide for combined drug and microRNA delivery and magnetic resonance imaging

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