PMID- 19783037 OWN - NLM STAT- MEDLINE DCOM- 20100125 LR - 20220317 IS - 1878-5905 (Electronic) IS - 0142-9612 (Linking) VI - 31 IP - 1 DP - 2010 Jan TI - Self-assembled hyaluronic acid nanoparticles for active tumor targeting. PG - 106-14 LID - 10.1016/j.biomaterials.2009.09.030 [doi] AB - 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. FAU - Choi, Ki Young AU - Choi KY AD - Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea. FAU - Chung, Hyunjin AU - Chung H FAU - Min, Kyung Hyun AU - Min KH FAU - Yoon, Hong Yeol AU - Yoon HY FAU - Kim, Kwangmeyung AU - Kim K FAU - Park, Jae Hyung AU - Park JH FAU - Kwon, Ick Chan AU - Kwon IC FAU - Jeong, Seo Young AU - Jeong SY LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090926 PL - Netherlands TA - Biomaterials JT - Biomaterials JID - 8100316 RN - 9004-61-9 (Hyaluronic Acid) SB - IM MH - Animals MH - *Drug Delivery Systems MH - Hyaluronic Acid/*administration & dosage MH - Mice MH - Microscopy, Confocal MH - *Nanoparticles MH - Neoplasms, Experimental/*drug therapy EDAT- 2009/09/29 06:00 MHDA- 2010/01/26 06:00 CRDT- 2009/09/29 06:00 PHST- 2009/08/18 00:00 [received] PHST- 2009/09/08 00:00 [accepted] PHST- 2009/09/29 06:00 [entrez] PHST- 2009/09/29 06:00 [pubmed] PHST- 2010/01/26 06:00 [medline] AID - S0142-9612(09)00960-0 [pii] AID - 10.1016/j.biomaterials.2009.09.030 [doi] PST - ppublish SO - Biomaterials. 2010 Jan;31(1):106-14. doi: 10.1016/j.biomaterials.2009.09.030. Epub 2009 Sep 26.