AS1411aptamer conjugated liposomes for targeted delivery of arsenic trioxide in mouse xenograft model of melanoma cancer

Abstract

Development and characterizing of AS1411aptamer conjugated liposomes for targeted delivery of arsenic trioxide is the primary goal of this study to increase the drug safety and efficacy in the treatment of solid tumors. The targeted liposomes were constructed by the thin film method, and arsenic trioxide was loaded as cobalt (II) hydrogen arsenite (CHA). The liposomal structure was examined by Fourier Transform Infra-red Spectroscopy and field emission scanning electron microscopy. In addition, particle sizes and zeta potential of the CHA-loaded liposomes (CHAL) and aptamer-functionalized CHA-loaded liposomes (AP-CHAL) were determined. An atomic absorption spectrometer was used to quantify the encapsulation efficiency and in vitro drug release. In vitro cytotoxicity of CHAL and AP-CHAL were evaluated using MTT assay in Murine melanoma (B16) and Mouse Embryonic Fibroblast cell lines. The encapsulation efficiency of CHAL and AP-CHAL was reported as 60.2 ± 6.5 % and 58.7 ± 4.2 %, respectively. The enhanced cellular uptake of aptamer-conjugated liposomes was displayed by Fluorescence imaging. In vivo antitumor activity of CHAL and AP-CHAL in the B16 tumor-xenograft mouse model was dramatically observed. All mice in the CHAL group survived to the end of treatment and showed body weight gain. However, the distinct antitumor effect was observed in the AP-CHAL-treated group, and the tumor protrusion completely disappeared in 50 % of the mice. The inhibition rate of tumor growth of CHAL and AP-CHAL was 92.73 % and 97.67 %, respectively. Furthermore, histopathology studies demonstrated that CHAL and AP-CHAL did not induce significant toxicity in mice tissues. AP-CHAL can be used as an effective drug delivery system with high potential in treating solid tumors.