Self-assembled hyaluronic acid nanoparticles for active tumor targeting

• Published in: Biomaterials Vol. 31; no. 1; pp. 106 - 114
• Main Authors: Choi, Ki Young, Chung, Hyunjin, Min, Kyung Hyun, Yoon, Hong Yeol, Kim, Kwangmeyung, Park, Jae Hyung, Kwon, Ick Chan, Jeong, Seo Young
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.01.2010
• Subjects: Active targeting; Advanced Basic Science; Animals; Dentistry; Drug Delivery Systems; Hyaluronic acid; Hyaluronic Acid - administration & dosage; Mice; Microscopy, Confocal; Nanoparticle; Nanoparticles; Neoplasms, Experimental - drug therapy; Passive targeting; Tumor specificity; Passive targeting; Active targeting; Tumor specificity; Hyaluronic acid; Nanoparticle
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2009.09.030

Abstract 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.