Block Copolymer-Templated Mineralization for pH-Responsive Robust Nanocarriers of 5-Fluorouracil

Gi Hyun Choi; Kyung Hyun Min; Sang Cheon

Macromolecular Research, Vol.22, No.3, 329-336, March, 2014

DOI10.1007/s13233-014-2042-9 Export Citation

Block Copolymer-Templated Mineralization for pH-Responsive Robust Nanocarriers of 5-Fluorouracil

Gi Hyun Choi, Kyung Hyun Min¹, and Sang Cheon^†

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, College of Pharmacy, Kyung Hee University, Seoul, 130-701, Korea

E-mail:

We describe a novel synthetic method to prepare calcium carbonate (CaCO3)-mineralized nanoparticles for the intracellular delivery of an anticancer drug, 5-fluorouracil (5-FU). The 5-FU-loaded mineralized nanoparticles(FU-CaCO3-MNPs) were prepared by block copolymer (poly(ethylene glycol)-b-poly(L-aspartic acid) (PEG-PAsp))-templated mineralization in the presence of calcium cations (Ca2+), carbonate anions (CO32-), and negatively charged 5-FU. The mineralization produced hybrid nanoparticles consisting of 5-FU-loaded CaCO3 cores and PEG shells. The mineralized CaCO3 cores of the nanoparticles could stably hold loaded 5-FU by maintaining the structural robustness, and the outer corona of PEG provided colloidal stability to the nanoparticles in serum solutions. The 5-FU release from the FU-CaCO3-MNPs at physiological pH (pH 7.4) was efficiently inhibited, whereas at an endosomal pH (pH 5.0), the 5-FU release was facilitated. Fluorescence microscopic analysis showed that FU-CaCO3-MNPs were taken up by the MCF-7 breast cancer cells, and transferred into acidic endosomes to dissolve the CaCO3 core. Finally, the 5-FU release was facilitated to inhibit the proliferation of cancer cells. These mineralized hybrid nanoparticles may serve as a useful candidate for enhanced intracellular delivery of many ionic anticancer drugs.

Keywords:mineralization;pH-sensitive;calcium carbonate;5-fluorouracil;intracellular release.

[References]

Choi KY, Yoon HY, Kim JH, Bae SM, Park RW, Kang YM, Kim IS, Kwon IC, Choi K, Jeong SY, ACS Nano., 5, 8591 (2011)
Sawant R, Hurley J, Salmaso S, Kale A, Tolcheva E, Levchenko T, Torchilin V, Bioconjug Chem., 17, 943 (2006)
Burakowska E, Zimmerman SC, Haag R, Small., 5, 2199 (2009)
Rejinold NS, Sreerekha PR, Chennazhi KP, Nair SV, Jayakumar R, Int. J. Biol. Macromol., 49, 161 (2011)
Hu P, Tirelli N, Bioconjug. Chem., 23, 438 (2012)
Fomina N, Sankaranarayanan J, Almutairi A, Adv. Drug Deliv. Rev., 64, 1005 (2012)
Han SY, Han HS, Lee SC, Kang YM, Kim IS, Park JH, J. Mater. Chem., 21, 7996 (2011)
Choi KY, Min KH, Yoon HY, Kim K, Park JH, Kwon IC, Choi K, Jeong SY, Biomaterials, 32, 1880 (2011)
Min KH, Lee HJ, Kim K, Kwon IC, Jeong SY, Lee SC, Biomaterials, 33, 5788 (2012)
Koo AN, Min KH, Lee HJ, Lee SU, Kim K, Kwon IC, Cho SH, Jeong SY, Lee SC, Biomaterials, 33, 1489 (2012)
Wu L, Zou Y, Deng C, Cheng R, Meng F, Zhong Z, Biomaterials, 34, 5262 (2013)
Shrestha R, Elsabahy M, Florez-Malaver S, Samarajeewa S, Wooley KL, Biomaterials, 33, 8557 (2012)
He H, Chen S, Zhou J, Dou Y, Song L, Che L, Zhou X, Chen X, Jia Y, Zhang J, Li S, Li X, Biomaterials, 34, 5344 (2013)
Tang R, Ji W, Panus D, Palumbo RN, Wang C, J. Control. Release, 151, 18 (2011)
Lee Y, Fukushima S, Bae Y, Hiki S, Ishii T, Kataoka K, J. Am. Chem. Soc., 129(17), 5362 (2007)
Lee SJ, Min KH, Lee HJ, Koo AN, Rim HP, Jeon BJ, Jeong SY, Heo JS, Lee SC, Biomacromolecules, 12(1224) (2011)
Lee HJ, Kim SE, Kwon IK, Park C, Kim C, Yang J, Lee SC, Chem. Commun., 46, 377 (2010)
Rim HP, Min KH, Lee HJ, Jeong SY, Lee SC, Angew. Chem. Int. Ed., 50, 8853 (2011)
Kakizawa Y, Furukawa S, Kataoka K, J. Control. Release, 97, 345 (2004)
Ogomi D, Serizawa T, Akashi M, J. Control. Release, 103, 315 (2005)
Parker WB, Cheng YC, Pharmacol. Ther., 48, 381 (1990)
Daly WH, Poche D, Tetrahedron Lett., 29, 5859 (1988)
Harada A, Kataoka K, Macromolecules, 31(2), 288 (1998)
Otsuka H, Nagasaki Y, Kataoka K, Adv. Drug Deliv. Rev., 64, 246 (2012)
Gross RA, Kalra B, Science, 297, 803 (2002)
Kondo M, Araie M, Invest. Ophthalmol. Vis. Sci., 30, 583 (1989)
Naka K, Tanaka Y, Chujo Y, Langmuir, 18(9), 3655 (2002)
Lee SC, Huh KM, Lee J, Cho YW, Galinsky RE, Park K, Biomacromolecules, 8(1), 202 (2007)
Goss SL, Lemons KA, Kerstetter JE, Bogner RH, J. Pharm. Pharmacol., 59, 1485 (2007)
Nido PJD, Glynn P, Buenaventura P, Salama G, Koretsky AP, Am. J. Physiol. Heart Circ. Physiol., 274, 728 (1998)
Fonteriz RI, Fuente SDI, Moreno A, Lobaton CD, Montero M, Alvarez J, Cell Calcium, 48, 61 (2010)

[Referenced By]

[1] Choi KY, Yoon HY, Kim JH, Bae SM, Park RW, Kang YM, Kim IS, Kwon IC, Choi K, Jeong SY, ACS Nano., 5, 8591 (2011)

[2] Sawant R, Hurley J, Salmaso S, Kale A, Tolcheva E, Levchenko T, Torchilin V, Bioconjug Chem., 17, 943 (2006)

[3] Burakowska E, Zimmerman SC, Haag R, Small., 5, 2199 (2009)

[4] Rejinold NS, Sreerekha PR, Chennazhi KP, Nair SV, Jayakumar R, Int. J. Biol. Macromol., 49, 161 (2011)

[5] Hu P, Tirelli N, Bioconjug. Chem., 23, 438 (2012)

[6] Fomina N, Sankaranarayanan J, Almutairi A, Adv. Drug Deliv. Rev., 64, 1005 (2012)

[7] Han SY, Han HS, Lee SC, Kang YM, Kim IS, Park JH, J. Mater. Chem., 21, 7996 (2011)

[8] Choi KY, Min KH, Yoon HY, Kim K, Park JH, Kwon IC, Choi K, Jeong SY, Biomaterials, 32, 1880 (2011)

[9] Min KH, Lee HJ, Kim K, Kwon IC, Jeong SY, Lee SC, Biomaterials, 33, 5788 (2012)

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

[11] Wu L, Zou Y, Deng C, Cheng R, Meng F, Zhong Z, Biomaterials, 34, 5262 (2013)

[12] Shrestha R, Elsabahy M, Florez-Malaver S, Samarajeewa S, Wooley KL, Biomaterials, 33, 8557 (2012)

[13] He H, Chen S, Zhou J, Dou Y, Song L, Che L, Zhou X, Chen X, Jia Y, Zhang J, Li S, Li X, Biomaterials, 34, 5344 (2013)

[14] Tang R, Ji W, Panus D, Palumbo RN, Wang C, J. Control. Release, 151, 18 (2011)

[15] Lee Y, Fukushima S, Bae Y, Hiki S, Ishii T, Kataoka K, J. Am. Chem. Soc., 129(17), 5362 (2007)

[16] Lee SJ, Min KH, Lee HJ, Koo AN, Rim HP, Jeon BJ, Jeong SY, Heo JS, Lee SC, Biomacromolecules, 12(1224) (2011)

[17] Lee HJ, Kim SE, Kwon IK, Park C, Kim C, Yang J, Lee SC, Chem. Commun., 46, 377 (2010)

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

[19] Kakizawa Y, Furukawa S, Kataoka K, J. Control. Release, 97, 345 (2004)

[20] Ogomi D, Serizawa T, Akashi M, J. Control. Release, 103, 315 (2005)

[21] Parker WB, Cheng YC, Pharmacol. Ther., 48, 381 (1990)

[22] Daly WH, Poche D, Tetrahedron Lett., 29, 5859 (1988)

[23] Harada A, Kataoka K, Macromolecules, 31(2), 288 (1998)

[24] Otsuka H, Nagasaki Y, Kataoka K, Adv. Drug Deliv. Rev., 64, 246 (2012)

[25] Gross RA, Kalra B, Science, 297, 803 (2002)

[26] Kondo M, Araie M, Invest. Ophthalmol. Vis. Sci., 30, 583 (1989)

[27] Naka K, Tanaka Y, Chujo Y, Langmuir, 18(9), 3655 (2002)

[28] Lee SC, Huh KM, Lee J, Cho YW, Galinsky RE, Park K, Biomacromolecules, 8(1), 202 (2007)

[29] Goss SL, Lemons KA, Kerstetter JE, Bogner RH, J. Pharm. Pharmacol., 59, 1485 (2007)

[30] Nido PJD, Glynn P, Buenaventura P, Salama G, Koretsky AP, Am. J. Physiol. Heart Circ. Physiol., 274, 728 (1998)

[31] Fonteriz RI, Fuente SDI, Moreno A, Lobaton CD, Montero M, Alvarez J, Cell Calcium, 48, 61 (2010)