Double Targeting, Controlled Release And Reversible Delivery Of Daunorubicin To Cancer Cells By Polyvalent Aptamers-Modified Gold Nanoparticles

Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children.Clinical use ofdaunorubicin (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 theirefficacy. 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 acutelymphoblastic leukemia T-cell, target). Dau was efficiently loaded (10.5 μ M)onto 1 mLof PAmodifiedAuNPs. Dau was released from the PA-Dau-AuNPs complex in a pH-sensitive manner(faster release at pH 5.5). The results of flowcytometry analysis indicated that the PA-Dau-AuNPscomplex was efficiently internalized into target cells, but not into non target cells. The results ofMTT assay were consistent with the internalization data. PA-Dau-AuNPs complex had lesscytotoxicity 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 antisenseof polyvalent aptamers. In conclusion, the designed drug delivery system inherited the propertiesof efficient drug loading, tumor targeting, pH-dependent drug release and controllable delivery ofDau to tumor cells. Furthermore, the cytotoxicity of PADau- AuNPs complex could efficiently beantagonized using the antisense of polyvalent aptamers.