Cholesteryl hyaluronic acid-coated, reduced graphene oxide nanosheets for anti-cancer drug delivery
2013
Miao, Wenjun | Shim, Gayong | Kang, Choong Mo | Lee, Soondong | Choe, Yearn Seong | Choi, Han-Gon | Oh, Yu-Kyoung
Here, we report hyaluronyl reduced graphene oxide (rGO) nanosheets as a tumor-targeting delivery system for anticancer agents. Hyaluronyl-modified rGO nanosheets were prepared by synthesizing cholesteryl hyaluronic acid (CHA) and using it to coat rGO nanosheets, yielding CHA-rGO. Compared with rGO, CHA-rGO nanosheets showed increased colloidal stability under physiological conditions and improved in vivo safety, with a survival rate of 100% after intravenous administration of 40 mg/kg in mice. The doxorubicin (Dox) loading capacity of CHA-rGO was 4-fold greater than that of rGO. Uptake of Dox by CD44-overexpressing KB cells was higher for CHA-rGO than for rGO, and was decreased in the presence of hyaluronic acid through competition for CD44 receptor binding. After intravenous administration in tumor-bearing mice, CHA-rGO/Dox showed higher tumor accumulation than rGO/Dox. The in vivo antitumor efficacy of Dox delivered by CHA-rGO was significantly increased compared with free Dox or rGO/Dox. In CHA-rGO/Dox-treated mice, tumor weights were reduced to 14.1% ± 0.1% of those in untreated mice. Our findings indicate that CHA-rGO nanosheets possess greater stability, safety, drug-loading capacity, and CD44-mediated delivery of Dox than rGO nanosheets. These beneficial properties of CHA-rGO improved the distribution of Dox to tumors and facilitated the cellular uptake of Dox by CD44-overexpressing tumor cells, resulting in enhanced anticancer effects.
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