Preparation and characterization of folic acid linked poly(L-glutamate) nanoparticles for cancer targeting
- 185 Downloads
- 22 Citations
Abstract
Nanoparticles of Poly(L-glutamic acid) (PG) conjugated to the anticancer drug paclitaxel and targeted moiety folic acid (FA) were synthesized and characterizedin 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 by1H-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 cellsin vitro.
Keywords
cancer targeting folate receptor nanoparticles PGPreview
Unable to display preview. Download preview PDF.
References
- (1).J. B. Gibbs,Science,287, 1969 (2000).CrossRefGoogle Scholar
- (2).D. Dube, M. Francis, J.-C. Leroux, and F. M. Winnik,Bioconjugate Chem.,13, 685 (2002).CrossRefGoogle Scholar
- (3).J. Sudimack and R. J. Lee,Adv. Drug Del. Rev.,41, 147 (2000).CrossRefGoogle Scholar
- (4).A. Tang, P. Kopeckova, and J. Kopecek,Pharm. Res.,20, 360 (2003).CrossRefGoogle Scholar
- (5).M. V. Backer and J. M. Backer,Bioconjugate Chem.,12, 1066 (2001).CrossRefGoogle Scholar
- (6).N. K. Egilmez, Y. S. Jong, M. S. Sabel, J. S. Jacob, E. Mathiowitz, and R. B. Bankert,Cancer Res.,60, 3832 (2000).Google Scholar
- (7).C. J. Mathias, D. Hubers, P. S. Low, and M. A.Green,Bioconjugate Chem.,11, 253 (2000).CrossRefGoogle Scholar
- (8).G. F. Rowland, G. J. O’Neill, and D. A. L. Davies,Nature,255, 487 (1975).CrossRefGoogle Scholar
- (9).J. Vega, S. Ke, Z. Fan, S. Wallace, C. Charsangave, and C. Li,Pharm. Res.,20, 826 (2003).CrossRefGoogle Scholar
- (10).P. Caliceti, S. Salmaso, A. Semenzato, T. Carofiglio, R. Fornasier, M. Fermeglia, M. Ferrone, and S. Pricl,Bioconjugate Chem.,14, 899 (2003).CrossRefGoogle Scholar
- (11).S. Wang, R. J. Lee, C. J. Mathias, M. A. Green, and P. S. Low,Bioconjugate Chem.,7, 56 (1996).CrossRefGoogle Scholar
- (12).K. Y. Lee,Macromol. Res.,13, 542 (2005).CrossRefGoogle Scholar
- (13).L. L. Kiessling, J. E.Gestwicki, and L. E. Strong,Curr. Opin. Chem. Biol.,4, 696 (2000).CrossRefGoogle Scholar
- (14).M. Mammen, S.-K. Choi, and G. M. Whitesides,Angew. Chem. Int. Ed. Engl.,37, 2754 (1998).CrossRefGoogle Scholar
- (15).D. M. Spencer, T. J. Wandless, S. L. Schreiber, and G. R. Crabtree,Science,262, 1019 (1993).CrossRefGoogle Scholar
- (16).C. R. Thomas and P. Bonomi,Curr. Opin. Oncol.,2, 359 (1990).CrossRefGoogle Scholar
- (17).R. Komaki, J. B. Putnam, and J. D. Shin Cox,Curr. Opin. Oncol.,9, 156 (1997).CrossRefGoogle Scholar
- (18).C. Li,Adv. Drug. Deliv. Rev.,54, 695 (2002).CrossRefGoogle Scholar
- (19).C. Li, J. E. Price, L. Milas, N. R. Hunter, S. Ke, D.-F. Yu, C. Charnsangavej, and S. Wallace,Clin. Cancer Res.,5, 891 (1999).Google Scholar
- (20).R. Duncan,Nature Rev. Drug Discov.,2, 347 (2003).CrossRefGoogle Scholar
- (21).W. Tansey, S. Ke, X.-Y. Cao, M. J. Pasuelo, S. Wallace, and C. Li,J. Control. Release,94, 39 (2004).CrossRefGoogle Scholar
- (22).T. J. Deming,Nature,390, 386 (1997).CrossRefGoogle Scholar
- (23).C. Li, D. F. Yu, R. A. Newman, F. Cabral, L. C. Stephens, N. Hunter, L. Milas, and S. Wallace,Cancer Res.,58, 2404 (1998).Google Scholar
- (24).C. P. Leamon, S. R. Cooper, and G. E. Hardee,Bioconjugate Chem.,14, 738 (2003).CrossRefGoogle Scholar