Double Targeting, Controlled Release and Reversible Delivery of Daunorubicin to Cancer Cells by Polyvalent Aptamers-Modified Gold Nanoparticles Publisher Pubmed



Taghdisi SM¹ ; Danesh NM^{2, 3} ; Lavaee P^{4, 5} ; Emrani AS⁶ ; Hassanabad KY⁷ ; Ramezani M² ; Abnous K⁸
Source: Materials Science and Engineering C Published:2016

Abstract

Clinical use of daunorubicin (Dau) in treatment of leukemia has been restricted because of its cardiotoxicity. Targeted delivery of anticancer drugs could decrease their off-target effects and enhance their efficacy. In this study a modified polyvalent aptamers (PA)-Daunorubicin (Dau)-Gold nanoparticles (AuNPs) complex was designed and its efficacy was assessed in Molt-4 cells (human acute lymphoblastic leukemia T-cell, target). Dau was efficiently loaded (10.5 μM) onto 1 mL of PA-modified AuNPs. Dau was released from the PA-Dau-AuNPs complex in a pH-sensitive manner (faster release at pH 5.5). The results of flow cytometry analysis indicated that the PA-Dau-AuNPs complex was efficiently internalized into target cells, but not into nontarget cells. The results of MTT assay were consistent with the internalization data. PA-Dau-AuNPs complex had less cytotoxicity in U266 cells compared to Dau alone and even Apt-Dau-AuNPs complex. The PA-Dau-AuNPs complex had more cytotoxicity in Molt-4 cells compared to Dau alone and even Apt-Dau-AuNPs complex. Cytotoxicity of PA-Dau-AuNPs complex was effectively antagonized using antisense of polyvalent aptamers. In conclusion, the designed drug delivery system inherited the properties of efficient drug loading, tumor targeting, pH-dependent drug release and controllable delivery of Dau to tumor cells. © 2016 Elsevier B.V. All rights reserved.