Self-assembled hyaluronic acid nanoparticles for active tumor targeting.
Hyaluronic acid nanoparticles (HA-NPs), which are formed by the self-assembly of hydrophobically modified HA derivatives, were prepared to investigate their physicochemical characteristics and fates in tumor-bearing mice after systemic administration. The particle sizes of HA-NPs were controlled in the range of 237-424 nm by varying the degree of substitution of the hydrophobic moiety. When SCC7 cancer cells over-expressing CD44 (the receptor for HA) were treated with fluorescently labeled Cy5.5-HA-NPs, strong fluorescence signals were observed in the cytosol of these cells, suggesting efficient intracellular uptake of HA-NPs by receptor-mediated endocytosis. In contrast, no significant fluorescence signals were observed when Cy5.5-labeled HA-NPs were incubated with normal fibroblast cells (CV-1) or with excess free-HA treated SCC7 cells. Following systemic administration of Cy5.5-labeled HA-NPs with different particle sizes into a tumor-bearing mouse, their biodistribution was monitored as a function of time using a non-invasive near-infrared fluorescence imaging system. Irrespective of the particle size, significant amounts of HA-NPs circulated for two days in the bloodstream and were selectively accumulated into the tumor site. The smaller HA-NPs were able to reach the tumor site more effectively than larger HA-NPs. Interestingly, the concentration of HA-NPs in the tumor site was dramatically reduced when mice were pretreated with an excess of free-HA. These results imply that HA-NPs can accumulate into the tumor site by a combination of passive and active targeting mechanisms.
Choi
Ki Young
KY
Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea.
Chung
Hyunjin
H
Min
Kyung Hyun
KH
Yoon
Hong Yeol
HY
Kim
Kwangmeyung
K
Park
Jae Hyung
JH
Kwon
Ick Chan
IC
Jeong
Seo Young
SY
D000818:Animals; D016503:Drug Delivery Systems; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D051379:Mice; D018613:Microscopy, Confocal; D053758:Nanoparticles; D009374:Neoplasms, Experimental / Q000188:drug therapy*
D006820:Hyaluronic Acid