Targeted Intracellular Heat Transfer in Cancer Therapy: Assessment of Asparagine-laminated Gold Nanoparticles in Cell Model of T cell Leukemia

Abstract

Background: High temperatures have destructive effects on cancer cells by damaging proteins and structures within cells. Gold nanoparticles (AuNPs) can act as drug delivery vehicles, especially for cancer therapy. Due to the selective intake of asparagine molecules into malignant cells, AuNPs were coated with asparagine; and CCRF-CEM human T-cell leukemia cells were treated with the new combination, Asn-AuNPs, at 39 °C. Methods: The co-authors from a number of collaborative labs located at Tehran University of Medical Sciences, Tehran, Iran, have initiated the idea and preliminary design of this study in 2011. Hydroxyl surfaced AuNPs were preliminary prepared by tannin free ethanol extract of black tea leaves. These biogenic AuNPs were further capped with asparagines to form asparagine-gold nanoparticle conjugates (Asn-AuNP conjugates). Then CCRF-CEM human T-cell leukemia cells were separately treated with different concentrations of AuNPs and Asn-AuNP conjugates (3, 30, 300 µg/mL). MTT assay and zymography analysis were carried out, and the apoptotic and necrotic effects of Asn-AuNPs were determined in comparison with AuNPs, using flow cytometry assay. Results: Asn-AuNP conjugates at 300 µg/mL significantly inhibited MMPs at 39 °C, compared to AuNPs. In terms of cytotoxicity, a remarkable decrease was observed in the percentage of viable cells treated with Asn-AuNP conjugates, rather than AuNPs. Moreover, the AuNPs and Asn-AuNP conjugates enhanced the level of apoptosis at almost similar rates. Conclusion: AuNPs are coated with asparagine molecules and the temperature is slightly increased by 2 °C, the apoptosis is not only enhanced among cells but also shifts to necrosis in higher concentrations of Asn-AuNP conjugates. More investigations should be carried out to explain the exact mechanism underlying the necrotic effects of Asn-AuNPs.

Keywords

• Gold nanoparticles
• Asparagine
• Acute lymphoblastic leukemia
• CCRF-CEM cells