Biorecognizable Nanoparticles Based On Hyaluronic Acid/Poly(ε-Caprolactone) Block Copolymer

Since hyaluronic acid (HA) receptor such as CD44 is
over-expressed at sites of cancer cells, HA can be used as a targeting
vehicles for anti-cancer drugs. The aim of this study is to synthesize
block copolymer composed of hyaluronic acid and
poly(ε-caprolactone) (HAPCL) and to fabricate polymeric micelles for
anticancer drug targeting against CD44 receptor of tumor cells.
Chemical composition of HAPCL was confirmed using 1H NMR
spectroscopy. Doxorubicin (DOX) was incorporated into polymeric
micelles of HAPCL. The diameters of HAPHS polymeric micelles
were changed around 80nm and have spherical shapes. Targeting
potential was investigated using CD44-overexpressing. When
DOX-incorporated polymeric micelles was added to KB cells, they
revealed strong red fluorescence color while blocking of CD44
receptor by pretreatment of free HA resulted in reduced intensity,
indicating that HAPCL polymeric micelles have targetability against
CD44 receptor.

• Jong Ho Hwang
• Dae Hwan Kang
• Young-IL Jeong

• Hyaluronic acid
• CD44 receptor
• biorecognizable nanoparticles
• block copolymer.

<p>[1] X. Huang, Y.I. Jeong, B.K. Moon, L. Zhang, D.H. Kang, I. Kim,
&quot;Self-assembly of morphology-tunable architectures from
tetraarylmethane derivatives for targeted drug delivery,&quot; Langmuir, vol.
29, no. 10, pp. 3223-3333, 2013.
[2] S. Xu, Q. Xu, J. Zhou, J. Wang, N. Zhang, L. Zhang, &quot;Preparation and
characterization of folate-chitosan-gemcitabine core-shell nanoparticles
for potential tumor-targeted drug delivery,&quot; J Nanosci. Nanotechnol. vol.
13, no. 1, pp. 129-138, 2013.
[3] Y. Bae, W.D. Jang, N. Nishiyama, S. Fukushima, K. Kataoka.
&quot;Multifunctional polymeric micelles with folate-mediated cancer cell
targeting and pH-triggered drug releasing properties for active
intracellular drug delivery,&quot; Mol. Biosyst. vol. 1, no. 3, pp. 242-250, 2005.
[4] V. Ladeda, J.A. Aguirre Ghiso, E. Bal de Kier Joffe, &quot;Function and
expression of CD44 during spreading, migration, and invasion of murine
carcinoma cells,&quot; Exp. Cell Res., vol. 242, pp. 515-527, 1998.
[5] Y. Akiyama, S. Jung, B. Salhia, S. Lee, S. Hubbard, M. Taylor, T.
Mainprize, K. Akaishi, W. Furth, J. T. Rutka, &quot;Hyaluronate receptors
mediating glioma cell migration and proliferation,&quot; J. Neuro-Oncol., vol.
53, pp. 115&ndash;127, 2001.
[6] E. Auzenne, S.C. Ghosh, M. Khodadadian, B. Rivera, D. Farquhar, R.E.
Price, M. Ravoori, V. Kundra, R.S. Freedman, J. Klostergaard,
&quot;Hyaluronic acid-paclitaxel: antitumor efficacy against CD44(+) human
ovarian carcinoma xenografts,&quot; Neoplasia, vol. 9, pp. 479-486, 2007.
[7] N. Senzer, J. Nemunaitis, D. Nemunaitis, C. Bedell, G. Edelman, M.
Barve, R. Nunan, K. F. Pirollo, A. Rait, E.H. Chang, &quot;Phase I study of a
systemically delivered p53 nanoparticle in advanced solid tumors,&quot; Mol
Ther. vol. 21, no. 5, pp. 1096-1103, 2013.
[8] Y.I. Jeong, D.H. Kim, C.W. Chung, J.J. Yoo, K.H. Choi, C.H. Kim, S.H.
Ha, D.H. Kang, &quot;Self-assembled nanoparticles of hyaluronic
acid/poly(DL-lactide-co-glycolide) block copolymer,&quot; Colloids Surf B
Biointerfaces. vol. 90, pp. 28-35, 2012.
[9] Y. Luo, G.D. Prestwich, &quot;Synthesis and selective cytotoxicity of a
hyaluronic acid&ndash;antitumor bioconjugate,&quot; Bioconj. Chem., vol. 10, pp.
755&ndash;763, 1999.
[10] Y. Luo, N.J. Bernshaw, Z.R. Lu, J. Kopecek, G.D. Prestwich, &quot;Targeted
delivery of doxorubicin by HPMA copolymer-hyaluronan
bioconjugates,&quot; Pharm. Res., vol. 19, pp. 396-402, 2002.
[11] E. Segawa, H. Kishimoto, K. Takaoka, K. Noguchi, S. Hashitani, K.
Sakurai, M. Urade, &quot;Promotion of hematogenous metastatic potentials in
human KB carcinoma cells with overexpression of cyclooxygenase-2,&quot;
Oncol. Rep. vol. 24, no. 3, pp. 733-739, 2010.</p>