Abstract
Molecular theranostics is of the utmost interest for diagnosis as well as treatment of different malignancies. In the present study, anionic linear globular dendrimer G2 is employed as a suitable carrier for delivery and AS1411 aptamer is exploited as the targeting agent to carry Iohexol specifically to the human breast cancer cells (MCF-7). Dendrimer G2 was prepared and conjugation of dendrimer and aptamer was carried out thereafter. Based on the data yielded by AFM, morphology of smooth and spherical non-targeted dendrimer changed to the rough aspherical shape when it conjugated. Then, conjugation was confirmed using DLS, ELS and SLS methods. Toxicity on nucleolin positive MCF-7 cells and nucleolin negative HEK-293 cells was assessed by XTT and apoptosis/necrosis assays. In vitro uptake was determined using DAPI-FITC staining and ICP-MS methods. In vivo studies including in vivo CT imaging, pathology and blood tests were done to confirm the imaging ability, bio-safety and targeted nature of the Nano-Theranostics in vivo. In a nutshell, the prepared construction showed promising effects upon decreasing the toxicity of Iohexol on normal cells and accumulation of it in the cancer tumors as well as reducing the number of cancer cells.
Highlights
There are numerous types of nanoparticles have been used in various studies up to now
In this research for the first time, controlled release, Iohexol cytotoxicity reduction on normal cells and targeting property to the cancer cells were employed by Anionic Linear Globular Dendrimer Generation 2 (ALGDG2) which is targeted by AS1411 aptamer to cancer cells
This study focused on diminishing the cytotoxicity of the conventional contrast media (Iohexol) on normal cells and reducing the dosage of the drug which is needed for the imaging process, using a low molecular weight, non-cytotoxic and negative charged nanoparticle (ALGDG2)
Summary
There are numerous types of nanoparticles have been used in various studies up to now (gold nanoparticles, silver nanoparticles, magnetic nanoparticles, dendrimers, etc.) These chemically synthesized compounds can trigger controlled release of materials (drugs, contrast agents, genes, etc.) they carry off, specific bio-distribution and targeting and abolish drug resistance[18]. Aptamer decorated nanoparticles, which can be bound to target cell-surface biomarkers through shape complementarity by way of non-covalent bonds, provide a sensitive and specific targeted drug delivery, imaging and diagnostic modalities for both in vitro and in vivo applications[27]. This study focused on diminishing the cytotoxicity of the conventional contrast media (Iohexol) on normal cells and reducing the dosage of the drug which is needed for the imaging process, using a low molecular weight, non-cytotoxic and negative charged nanoparticle (ALGDG2)
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