Development of a new micellar anticancer drug: Cationic polymer/vitamin A conjugate covered with hyaluronic acid
Tóm tắt
This study examined the development of a new micellar drug (MD) prepared from polyethylenimine (PEI)/vitamin A (all trans-retinoic acid; ATRA) conjugate (PeRA) for the treatment of cancer. To endow specific toxicity to cancer cells, PeRA was coated with hyaluronic acid (anionic polymer; HA), which enhanced the biocompatibility of PeRA and was easily degraded by the enzyme secreted from the tumor site. The physicochemical results suggest that HA covered the micelles well via a charge-charge interaction. The cytotoxicity of PeRA measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay varied according to the presence or absence of the HA degrading enzyme (HAase). When the enzyme was absent, PeRA-HA showed lower cytotoxicity against cancer cells but the cytotoxicity was increased dramatically in the presence of the HAase. To define the cytotoxic mechanism, the interactions between PeRA and the cells were observed by flow cytometry (FACS) and confocal microscopy. The results showed that nano-hole formation induces cytotoxicity via an electrostatic interaction between PeRA and cell surfaces. This suggests that a HA shielded PEI micelle system might be a viable alternative for the development of anticancer agents.
Tài liệu tham khảo
S. Nimesh, et al., J. Control. Release, 110, 457 (2006).
D. Goula, et al., Gene Therapy, 5, 1291 (1998).
W. Tiyaboonchai, J. Woiszwillo, and C. Middaugh, J. Pharm. Sci., 90, 902 (2001).
P. Erbacher, et al., J. Gene Med., 1, 210 (1999).
D. Yin, et al., Macromol. Res., 17, 19 (2009).
M. Lecocq, et al., Biochem. Biophys. Res. Commun., 278, 414 (2000).
L. Wightman, et al., J. Gene Med., 3, 362 (2001).
N. Chansri, et al., Pharm. Res., 25, 428 (2008).
F. Vizoso, et al., Eur. J. Surg. Oncol., 30, 318 (2004).
V. Lokeshwar, et al., Cancer Res., 56, 651 (1996).
S. Paris, et al., Eur. J. Cancer, 42, 3253 (2006).
D. Peer and R. Margalit, Int. J. Cancer, 108, 780 (2003).
J. Lesley, et al., J. Biol. Chem., 275, 26967 (2000).
D. Yin, et al., Cancer Lett., 243, 71 (2006).
M. Slevin, et al., Matrix Biol., 26, 58 (2007).
J. Lee and A. Spicer, Curr. Opin. Cell Biol., 12, 581 (2000).
Y. Matsui, et al., Gastrointest. Endosc., 60, 539 (2004).
S. Jaracz, et al., Bioorgan. Med. Chem., 13, 5043 (2005).
T. Ito, et al., J. Control. Release, 112, 382 (2006).
R. Stern, Pathol. Biol., 53, 372 (2005).
K. Girish and K. Kemparaju, Life Sci., 80, 1921 (2007).
K. Kudo and A. Tu, Arch. Biochem. Biophys., 386, 154 (2001).
N. Chang, Am. J. Physiol. Cell Phy., 273, C1987 (1997).
P. Chambon, FASEB J., 10, 940 (1996).
B. Klaholz, A. Mitschler, and D. Moras, J. Mol. Biol., 302, 155 (2000).
R. Lotan, Environ. Health Persp., 105, 985 (1997).
K. Park, et al., Biomaterials, 30, 2642 (2009).
D. Kim, et al., Macromol. Res., 14, 66 (2006).
K. Kim, et al., Macromol. Res., 16, 169 (2008).
Y. Umebayashi, et al., J. Biochem., 134, 219 (2003).
D. Fischer, et al., Biomaterials, 24, 1121 (2003).
K. Torres and S. Horwitz, Cancer Res., 58, 3620 (1998).
J. Manfredi and S. Horwitz, Pharmacol. Therapeut., 25, 83(1984).
A. Sparreboom, et al., Proc. Natl. Acad. Sci. U.S.A., 94, 2031 (1997).
B. Greiner, et al., J. Clin. Invest., 104, 147 (1999).
S. Hong, et al., Bioconjug. Chem., 17, 728 (2006).
A. Mecke, et al., Langmuir, 21, 8588 (2005).
T. Segura and L. Shea, Annu. Rev. Mater. Sci., 31, 25 (2001).
M. Davis, Curr. Opin. Biotech., 13, 128 (2002).
S. Hong, et al., Bioconjug. Chem., 15, 774 (2004).
H. Moroson, Cancer Res., 31, 373 (1971).
D. Liu, et al., Proc. Natl. Acad. Sci. U.S.A., 93, 7832 (1996).
J. K. Han, M. S. Kim, D. S. Lee, Y.-S. Kim, R.-W. Park, K. Kim, and I. C. Kwon, Macromol. Res., 17, 99 (2009).
J. Ki, J. Lee, and D. Park, Macromol. Res., 16, 66 (2008).
J. Park and Y. Cho, Macromol. Res., 15, 513 (2007).