Targeted and controlled release delivery of daunorubicin to T-cell acute lymphoblastic leukemia by aptamer-modified gold nanoparticles

Clinical administration of daunorubicin (Dau) in treatment of leukemia has been limited by its cardiotoxicity. Targeted delivery of chemotherapy drugs could reduce their side effects and increase the therapeutic efficacy of these drugs. Biocompatibility and large surface area of gold nanoparticles (AuNPs) make these nanoparticles great candidates for biomedical applications. In this study sgc8c aptamer (Apt)-Dau-AuNPs complex was designed and evaluated for treatment of Molt-4 cells (human acute lymphoblastic leukemia T-cell, target). Apt-Dau-AuNPs complex formation was analyzed by fluorometric analysis and gel retardation assay. Dau release profiles from the complex were evaluated in pHs 5.5 and 7.4. For cytotoxic studies (MU assay) U266 (B lymphocyte human myeloma, nontarget) and Molt-4 cells (target) were treated with Dau Apt-Dau conjugate and Apt-Dau-AuNPs complex. Internalization was monitored by flow cytometry and confocal imaging. 12 mu M Dau was efficiently loaded onto 1 mL of Apt-modified AuNPs. Dau was released from the complex in a pH-dependent manner (higher rate of release at pH 5.5). The results of flow cytometry analysis and confocal imaging showed that the complex was effectively internalized into Molt-4 cells, but not into U266 cells. The results of MU assay also confirmed the internalization data. Apt-Dau-AuNPs complex was less cytotoxic in U266 cells compared to Dau alone and even Apt-Dau conjugate. The complex was more cytotoxic in target cells in comparison with Dau alone and even Apt-Dau conjugate. In conclusion, Apt-Dau-AuNPs complex was able to selectively target Molt-4 cells. Another advantage of this system was pH-dependent release of drug from the complex. Furthermore, this complex has characteristics which make it ideal for clinical use. (C) 2015 Elsevier B.V. All rights reserved.