Preparation and Characterization of Folic Acid Linked Poly(L-glutamate) Nanoparticles for Cancer Targeting

Yong-kyu Lee

Macromolecular Research, Vol.14, No.3, 387-393, June, 2006

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Preparation and Characterization of Folic Acid Linked Poly(L-glutamate) Nanoparticles for Cancer Targeting

Yong-kyu Lee^†

Department of Chemical and Biological Engineering, Chungju National University, Chungbuk 380-702, Korea

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Nanoparticles of Poly(L-glutamic acid) (PG) conjugated to the anticancer drug paclitaxel and targeted moiety folic acid (FA) were synthesized and characterized in vitro. The nanoparticles were designed to take advantage of FA targeting to folate receptor (FR) positive cancer cells. The chemical composition of the conjugate was characterized by 1H-NMR, FTIR and UV/vis spectroscopy. The selective cytotoxicity of the FA-PG-paclitaxel conjugates was evaluated in FR positive cancer cells. The interaction of the conjugate was visualized by fluorescence microscopy with results confirming the successful preparation of the conjugate and the production of nanoparticles of about 200-300 nm in diameter. The amount of paclitaxel conjugated to FA-PG was 25% by weight. Cellular uptake of the conjugate was FA dependent, and the conjugate uptake was mediated specifically by the folate receptor. These results demonstrate the improved selective toxicity and effective delivery of an anticancer drug into FR bearing cells in vitro.

Keywords:cancer targeting;folate receptor;nanoparticles;PG

[References]

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[Referenced By]

[1] Gibbs JB, Science, 287(5460), 1969 (2000)

[2] Dube D, Francis M, Leroux JC, Winnik FM, Bioconjugate Chem., 13, 685 (2002)

[3] Sudimack J, Lee RJ, Adv. Drug Deliv. Rev., 41, 147 (2000)

[4] Tang A, Kopeckova P, Kopecek J, Pharm. Res., 20, 360 (2003)

[5] Backer MV, Backer JM, Bioconjugate Chem., 12, 1066 (2001)

[6] Egilmez NK, Jong YS, Sabel MS, Jacob JS, Mathiowitz E, Bankert RB, Cancer Res., 60, 3832 (2000)

[7] Mathias CJ, Hubers D, Low PS, Green MA, Bioconjugate Chem., 11, 253 (2000)

[8] Rowland GF, ONeill GJ, Davies DAL, Nature, 255, 487 (1975)

[9] Vega J, Ke S, Fan Z, Wallace S, Charsangave C, Li C, Pharm. Res., 20, 826 (2003)

[10] Caliceti P, Salmaso S, Semenzato A, Carofiglio T, Fornasier R, Fermeglia M, Ferrone M, Pricl S, Bioconjugate Chem., 14, 899 (2003)

[11] Wang S, Lee RJ, Mathias CJ, Green MA, Low PS, Bioconjugate Chem., 7, 56 (1996)

[12] Lee KY, Macromol. Res., 13(6), 542 (2005)

[13] Kiessling LL, Gestwicki JE, Strong LE, Curr. Opin. Chem. Biol., 4, 696 (2000)

[14] Mammen M, Choi SK, Whitesides GM, Angew. Chem.-Int. Edit. Engl, 37, 2754 (1998)

[15] Spencer DM, Wandless TJ, Schreiber SL, Crabtree GR, Science, 262, 1019 (1993)

[16] Thomas CR, Bonomi P, Curr. Opin. Oncol., 2, 359 (1990)

[17] Komaki R, Putnam JB, Shin JD, Curr. Opin. Oncol., 9, 156 (1997)

[18] Li C, Adv. Drug Deliv. Rev., 54, 695 (2002)

[19] Li C, Price JE, Milas L, Hunter NR, Ke S, Yu DF, Charnsangavej C, Wallace S, Clin. Cancer Res., 5, 891 (1999)

[20] Duncan R, Nature Rev. Drug Discov., 2, 347 (2003)

[21] Tansey W, Ke S, Cao XY, Pasuelo MJ, Wallace S, Li C, J. Control. Release, 94, 39 (2004)

[22] Deming TJ, Nature, 390(6658), 386 (1997)

[23] Li C, Yu DF, Newman RA, Cabral F, Stephens LC, Hunter N, Milas L, Wallace S, Cancer Res., 58, 2404 (1998)

[24] Leamon CP, Cooper SR, Hardee GE, Bioconjugate Chem., 14, 738 (2003)