Cancer cell specific targeting of nanogels from acetylated hyaluronic acid with low molecular weight.
In order to develop a novel self-assembly as a means of cancer cell targeting, self-organized nanogels were prepared from acetylated hyaluronic acid with low molecular weight (AC-HA(LM)). Three samples were obtained (AC-HA(LM)1, 2 and 3) with degrees of acetylation, 0.8, 2.1, or 2.6 acetyl groups per unit (2 glucose rings) of HA(LM) to control their hydrophobicity. The mean diameters of AC-HA(LM)2 and 3 were less than 300 nm with unimodal size distribution, while that of AC-HA(LM)1 was above 400 nm. The critical aggregation concentrations (CAC) of the nanogels in distilled water were < 1 x 10(-1) mg/mL. The doxorubicine (DOX) loading efficiencies and loading contents of AC-HA(LM) increased as the degree of acetylation increased, in particular, the loading efficiency of AC-HA(LM)3 reached above 90%. AC-HA(LM)3 nanogels showed IC(50) at 1300 ng/mL of the DOX concentration against HeLa cells (with HA-binding receptors) similar to free DOX. For monitoring of specific interaction with a carcinoma cell line (HeLa cells with HA-binding receptors), AC-HA(LM)3 was labeled with FITC and observed with a confocal microscope. HeLa cells were strongly luminated by interactions with fluorescence-labeled AC-HA(LM)3 nanogels; however, this luminance was significantly decreased by competition inhibition of free HA. This result indicates that modified HA maintains the ability to interact with HA-binding receptors. The selective cytotoxicity and interaction of AC-HA(LM) nanogels may help reduce side effects of anti-cancer drugs in clinical use.
Park
Wooram
W
Department of Biotechnology, The Catholic University of Korea, 43-1 Yeokkok 2-dong, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea.
Kim
Kyoung Sub
KS
Bae
Byoung-Chan
BC
Kim
Young-Heui
YH
Na
Kun
K
D000107:Acetylation; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*; D001667:Binding, Competitive; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004317:Doxorubicin / Q000008:administration & dosage / Q000032:analysis / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D005782:Gels; D006367:HeLa Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D020128:Inhibitory Concentration 50; D008970:Molecular Weight; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D009994:Osmolar Concentration; D010316:Particle Size; D014709:Vero Cells
D000970:Antineoplastic Agents; C497483:CD44 protein, human; D005782:Gels; D018960:Hyaluronan Receptors; D004317:Doxorubicin; D006820:Hyaluronic Acid