Glutathione-mediated intracellular release of anti-inflammatory N-acetyl-L-cysteine from mesoporous silica nanoparticles

Ahn Na Koo; Hwa Pyeong Rim; Dong Jin Park; Jong-Ho Kim; Seo Young Jeong; Sang Cheon Lee

Macromolecular Research, Vol.21, No.7, 809-814, July, 2013

DOI10.1007/s13233-013-1082-x Export Citation

Glutathione-mediated intracellular release of anti-inflammatory N-acetyl-L-cysteine from mesoporous silica nanoparticles

Ahn Na Koo, Hwa Pyeong Rim¹, Dong Jin Park¹, Jong-Ho Kim^{2, †}, Seo Young Jeong¹, and Sang Cheon Lee^†

Department of Maxillofacial Biomedical Engineering & Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul, 130-701, Korea
¹Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul, 130-701, Korea
²Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, 130-701, Korea

E-mail:,

We report on a smart mesoporous silica nanoparticle (MSN) that can trigger the release of anti-inflammatory N-acetyl-L-cysteine (NAC) within the intracellular environment. NAC was conjugated to the pore surfaces of MSNs through glutathione (GSH)-cleavable disulfide linkages. Solid-state nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR) spectroscopy, and Brunauer-Emmett-Teller (BET) analyses confirmed the successful NAC conjugation to the pore walls. The release of NAC from the NAC-conjugated MSN (MSN-NAC) could be controlled by adjusting the concentration of GSH regarding the release media. At an extracellular level of GSH (10 μM), the NAC release was greatly inhibited, whereas, at an intracellular level of GSH (2 mM), MSN-NAC facilitated the release of NAC. Confocal laser scanning microscopy (CLSM) studies showed that the NAC release was effectively triggered by intracellular GSH after uptake by BV-2 microglial cells. The MSN developed in this work may serve as the efficient intracellular carriers of NAC for the treatment of neuroinflammation.

Keywords:N-acetyl-L-cysteine;mesoporous silica nanoparticle;glutathione;intracellular release;neuroinflammation

[References]

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Yip L, Dart RC, Hurlbut KM, Crit. Care Med., 26, 40 (1998)
Koo AN, Min KH, Lee HJ, Lee SU, Kim K, Kwon IC, Cho SH, Jeong SY, Lee SC, Biomaterials, 33, 1489 (2012)
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Mortera R, Vivero-Escoto J, Slowing II, Garrone E, Onida B, Lin VSY, Chem. Commun., 45, 3219 (2009)
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Min KJ, Jou I, Joe E, Biochem. Biophys. Res. Commun., 312(4), 969 (2003)
Flora SJ, Poande M, Kannan G, Mehta A, Cell Mol. Biol., 50, 543 (2004)
Roy A, Jana A, Yatich K, Freidt MB, Fung YK, Martinson JA, Pahan K, Free Radic. Biol. Med., 45, 686 (2008)
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[Referenced By]

[1] Vivero-Escoto JL, Slowing II, Wu CW, Lin VSY, J. Am. Chem. Soc., 129, 3462 (2009)

[2] Zhu Y, Shi J, Shen W, Dong X, Feng J, Ruan M, Li Y, Angew. Chem.-Int. Edit., 44, 5083 (2005)

[3] Rim HP, Min KH, Lee HJ, Jeong SY, Lee SC, Angew. Chem.-Int. Edit., 50, 8853 (2011)

[4] Slowing I, Trewyn BG, Lin VSY, J. Am. Chem. Soc., 128(46), 14792 (2006)

[5] Park HS, Kim CW, Lee HJ, Choi JH, Lee SG, Yun YP, Kwon IC, Lee SJ, Jeong SY, Lee SC, Nanotechnology, 21, 225101 (2010)

[6] Slowing II, Trewyn BG, Lin VSY, J. Am. Chem. Soc., 129(28), 8845 (2007)

[7] Ferrari G, Yan CY, Greene LA, J. Neurosci., 15, 2857 (1995)

[8] Beichert M, Nebe CT, Hack V, Edler L, Droge W, Pittack N, Daniel V, Breitkreutz R, Schuster D, Brust J, J. Mol. Med., 78, 55 (2000)

[9] Wang B, Navath RS, Romero R, Kannan S, Kannan R, Int. J. Pharm., 377, 159 (2009)

[10] Dilger RN, Toue S, Kimura T, Sakai R, Baker DH, J. Nutr., 322, 331 (2007)

[11] Harada D, Naito S, Otagiri M, Pharm. Res., 19, 1648 (2002)

[12] Yip L, Dart RC, Hurlbut KM, Crit. Care Med., 26, 40 (1998)

[13] Koo AN, Min KH, Lee HJ, Lee SU, Kim K, Kwon IC, Cho SH, Jeong SY, Lee SC, Biomaterials, 33, 1489 (2012)

[14] Koo AN, Lee HJ, Kim SE, Chang JH, Park C, Kim C, Park JH, Lee SC, Chem. Commun., 44, 6570 (2008)

[15] Navath RS, Kurtoglu YE, Wang B, Kannan S, Romero R, Kannan RM, Bioconjugate Chem., 19, 2446 (2008)

[16] Kurtoglu YE, Navath RS, Wang B, Kannan S, Romero R, Kannan R, Biomaterials, 30, 2112 (2009)

[17] Mortera R, Vivero-Escoto J, Slowing II, Garrone E, Onida B, Lin VSY, Chem. Commun., 45, 3219 (2009)

[18] Hong R, Han G, Fernandez JM, Kim BJ, Forbes NS, Rotello VM, J. Am. Chem. Soc., 128(4), 1078 (2006)

[19] Anderson ME, Meister A, Anal. Biochem., 183, 16 (1989)

[20] Min KJ, Jou I, Joe E, Biochem. Biophys. Res. Commun., 312(4), 969 (2003)

[21] Flora SJ, Poande M, Kannan G, Mehta A, Cell Mol. Biol., 50, 543 (2004)

[22] Roy A, Jana A, Yatich K, Freidt MB, Fung YK, Martinson JA, Pahan K, Free Radic. Biol. Med., 45, 686 (2008)

[23] Paintlia MK, Paintlia AS, Contreras MA, Singh I, Singh AK, Exp. Neurol., 210, 560 (2008)

[24] Kumar KH, Khanum F, Cell Mol. Neurobiol., 33, 5 (2013)