Reversible targeting and controlled release delivery of daunorubicin to cancer cells by aptamer-wrapped carbon nanotubes

Abstract

Aim: Single-walled carbon nanotubes (SWNTs) have been already used as drug carriers. In this study, we introduced sgc8c aptamer (this aptamer targets leukemia biomarker protein tyrosine kinase-7) to complex between Dau (daunorubicin) and SWNT to enhance targeted delivery of Dau to acute lymphoblastic leukemia T-cells (Molt-4).

Material and methods: Dau-aptamer-SWNTs tertiary complex formation was analyzed by visible spectroscopy and spectrofluorophotometric analysis. Dau release profiles from the complex were investigated in pH 7.4 and 5.5. For cytotoxic studies (MTT assay), Molt-4 (target) and U266 (B lymphocyte human myeloma, non-target) cells were treated with Dau, Dau-aptamer-SWNTs tertiary complex. Internalization was analyzed by flow cytometry. Targeted delivery of Dau was antagonized using antisense of aptamer.

Results: Dau was efficiently loaded onto SWNTs (efficiency ∼ 157%). Dau was released from Dau-aptamer-SWNTs tertiary complex in a pH-dependent manner (higher release rate at pH 5.5). Flow cytometric analysis showed that the tertiary complex was internalized effectively to Molt-4 cells, but not to U266 cells. Cytotoxicity of Dau-aptamer-SWNTs tertiary complex also confirmed internalization data. Dau-aptamer-SWNTs tertiary complex was less cytotoxic in U266 cells when compared to Dau alone. No significant change in viability between Dau- and complex-treated Molt-4 cells was observed. Cytotoxicity of Dau-aptamer-SWNTs complex was efficiently and quickly reversed using antisense in Molt-4 cells.

Conclusion: Dau-aptamer-SWNTs complex is able to selectively target Molt-4 cells. The other advantages of this system are reversibility and pH-dependent release of Dau from its complex.