Tumor-specific hyperthermia with aptamer-tagged superparamagnetic nanoparticles

Abstract

Targeted therapy is a method owing to its limited side effect profile, particularly in cancer treatment. Magnetic hyperthermia, which is induced by nanoparticles (NPs) conjugated with targeting agents, can be useful in combination with chemo- or radiotherapy. In this paper, we constructed dextran-coated ferric oxide NPs conjugated with specific anti-human epidermal growth factor receptor (HER2) aptamer and used them to induce magnetic hyperthermia in cultured cells. The specificity of the tagged NPs was determined by studying their effect relative to that of non-tagged NPs against two cell lines: human adenocarcinoma SK-BR3, overexpressing the HER2 receptor; and U-87 MG, a human glioblastoma epithelial cell line, not expressing HER2. In order to confirm the interaction of the tagged NPs with the cells we used, fluorescence microscopy and fluorescence-activated cell sorting analysis were performed. All of these experiments showed that the aptamer-tagged NPs were highly specific toward the HER2-expressing cells. In addition, a ninetyfold lower dose of the tagged NPs relative to that of the non-tagged NPs was needed to achieve ~50% cell killing by hyperthermia of the SK-BR3 cell line, while for the U-87 MG cells the viability level was close to 100%. These results show that targeted NPs can be applied at substantially lower doses than non-targeted ones to achieve similar effects of hyperthermia, which should greatly limit the side effects of treatment.

Anti-FGFR1 aptamer-tagged superparamagnetic conjugates for anticancer hyperthermia therapy

“…The results are convergent with our previous studies, 26 which show that targeted nanoparticles specifically destroy targetexpressing cells upon irradiation with an ACMF, while not inflicting any significant damage on control cells.…”

“…[23][24][25] The relative ease and speed of their selection using the SELEX technique, their favorable properties (such as reversible denaturation, stability in various conditions, no batch-to-batch variation, ease and low price of large-scale chemical synthesis and versatility of chemical modification) and their effectiveness make aptamers a useful and promising tool for molecular diagnostics, therapeutics and research applications. As shown by Pala et al, 26 a strong and specific targeting DNA aptamer can increase the in vitro efficiency of hyperthermia by requiring over a 90-fold lower nanoparticle concentration for the same lethal effect obtained in a non-targeted fashion.…”

Magnetic Nanoparticle-Mediated Hyperthermia and Induction of Anti-Tumor Immune Responses

“…MNPs were conjugated with mAb against human breast cancer cells [25], human mAb against renal cell carcinoma [26], humanized mAb against human epidermal growth factor receptor-2 (HER2) [27] or its aptamer [28], and mAb against epidermal growth factor receptor (EGFR) [29]. When such nanoparticles were administrated systemically, they could accumulate specifically within tumors in animal models [25,26,29].…”

Applications of phototheranostic nanoagents in photodynamic therapy

“…Aptamers have potential uses both as therapeutic and targeting agents [153]. Like peptides, aptamers fold into complex three-dimensional structures that are highly specific to their targets [151][152][153][154][155][156].…”