RESUMO
In the current study, the synthesis of a theranostic platform composed of superparamagnetic iron oxide nanoparticles (SPION)-deferasirox conjugates targeted with AS1411 DNA aptamer was reported. In this regard, SPION was amine-functionalized by (3-aminopropyl)trimethoxysilane (ATPMS), and then deferasirox was covalently conjugated onto its surface. Finally, to provide guided drug delivery to cancerous tissue, AS1411 aptamer was conjugated to the complex of SPION-deferasirox. The cellular toxicity assay on CHO, C-26 and AGS cell lines verified higher cellular toxicity of targeted complex in comparison with non-targeted one. The evaluation of in vivo tumor growth inhibitory effect in C26 tumor-bearing mice illustrated that the aptamer-targeted complex significantly enhanced the therapeutic outcome in comparison with both non-targeted complex and free drug. The diagnostic capability of the prepared platform was also evaluated implementing C26-tumor-bearing mice. Obtained data confirmed higher tumor accumulation and higher tumor residence time for targeted complex through MRI imaging due to the existence of SPION as a contrast agent in the core of the prepared complex. The prepared multimodal theranostic system provides a safe and effective platform for fighting against cancer.
Assuntos
Antineoplásicos/uso terapêutico , Meios de Contraste/uso terapêutico , Deferasirox/uso terapêutico , Quelantes de Ferro/uso terapêutico , Nanopartículas de Magnetita/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/síntese química , Aptâmeros de Nucleotídeos/química , Células CHO , Linhagem Celular Tumoral , Meios de Contraste/síntese química , Cricetulus , Deferasirox/química , Feminino , Humanos , Ácidos Nucleicos Imobilizados/química , Ácidos Nucleicos Imobilizados/uso terapêutico , Quelantes de Ferro/síntese química , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Nanopartículas de Magnetita/química , Camundongos Endogâmicos BALB C , Medicina de Precisão , Propilaminas/química , Silanos/químicaRESUMO
Spherical nucleic acids (SNAs) represent an emerging class of nanoparticle-based therapeutics. SNAs consist of densely functionalized and highly oriented oligonucleotides on the surface of a nanoparticle which can either be inorganic (such as gold or platinum) or hollow (such as liposomal or silica-based). The spherical architecture of the oligonucleotide shell confers unique advantages over traditional nucleic acid delivery methods, including entry into nearly all cells independent of transfection agents and resistance to nuclease degradation. Furthermore, SNAs can penetrate biological barriers, including the blood-brain and blood-tumor barriers as well as the epidermis, and have demonstrated efficacy in several murine disease models in the absence of significant adverse side effects. In this chapter, we will focus on the applications of SNAs in cancer therapy as well as discuss multimodal SNAs for drug delivery and imaging.