Double targeting, controlled release and reversible delivery of daunorubicin to cancer cells by polyvalent aptamers-modified gold nanoparticles

Materials Science & Engineering. C, Materials for Biological Applications
Seyed Mohammad TaghdisiKhalil Abnous

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 1mL of PA-modified AuNPs. Dau was released from the PA-Dau-AuNPs complex in a pH-sensitive manner (faster release at pH5.5). 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 efficien...Continue Reading

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