Targeting heat shock protein 70 using gold nanorods enhances cancer cell apoptosis in low dose plasmonic photothermal therapy

• Published in: Biomaterials Vol. 102; pp. 1 - 8
• Main Authors: Ali, Moustafa R.K., Ali, Hala R., Rankin, Carl R., El-Sayed, Mostafa A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.09.2016
• Subjects: Advanced Basic Science; ambient temperature; antineoplastic activity; Apoptosis; Biotechnology; Cancer; Cell Line, Tumor; Cellular; Dentistry; epithelium; gene expression regulation; Gold; Gold - chemistry; Gold - therapeutic use; Gold nanorods (AuNRs); heat; Heat shock protein 70 (HSP70); heat tolerance; heat-shock protein 70; HSP70 Heat-Shock Proteins - metabolism; Humans; Hyperthermia, Induced - methods; liver; MCF-7 Cells; nanoparticles; Nanorods; Nanotubes - chemistry; Nanotubes - ultrastructure; necrosis; neoplasms; Neoplasms - metabolism; Neoplasms - therapy; Phototherapy - methods; Plasmonic photothermal therapy (PPTT); Plasmonics; Protein refolding; quercetin; Quercetin (QE); small interfering RNA; therapeutics; Therapy; viability; Plasmonic photothermal therapy (PPTT); Quercetin (QE); Heat shock protein 70 (HSP70); Protein refolding; Gold nanorods (AuNRs)
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2016.06.017

Plasmonic photothermal therapy (PPTT) is a promising cancer treatment where plasmonic nanoparticles are used to convert near infrared light to localized heat to cause cell death, mainly via apoptosis and necrosis. Modulating PPTT to induce cell apoptosis is more favorable than necrosis. Herein, we used a mild treatment condition using gold nanorods (AuNRs) to trigger apoptosis and tested how different cell lines responded to it. Three different cancer cell lines of epithelial origin: HSC (oral), MCF-7 (breast) and Huh7.5 (liver) had comparable AuNRs uptake and were heated to same environmental temperature (under 50 °C). However, Huh7.5 cells displayed a significant increase in cell apoptosis after PPTT as compared to the other two cell lines. As HSP70 is known to increase cellular resistance to heat, we determined relative HSP70 levels in these cells and results indicated that Huh7.5 cells had ten-fold decreased levels of HSP70 as compared with HSC and MCF-7 cells. We then down-regulated HSP70 with a siRNA and observed that all three cell lines displayed significant reduction in viability and an increase in apoptosis after PPTT. As an enhancement to PPTT, we conjugated AuNRs with Quercetin, an inhibitor of HSP70 which displayed anti-cancer effects via apoptosis.