Targeting heat shock protein 70 using gold nanorods enhances cancer cell apoptosis in low dose plasmonic photothermal therapy.
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.
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA.
Moustafa R K
MR
Ali
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA.
Hala R
HR
Ali
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA.
Carl R
CR
Rankin
School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA; School of Chemistry, King Abdul Aziz University, Saudi Arabia. Electronic address: melsayed@gatech.edu.
Mostafa A
MA
El-Sayed
D017209:Apoptosis; D045744:Cell Line, Tumor; D006046:Gold / Q000737:chemistry / Q000627:therapeutic use*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods; D061986:MCF-7 Cells; D043942:Nanotubes / Q000737:chemistry / Q000648:ultrastructure; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D010789:Phototherapy / Q000379:methods
D018840:HSP70 Heat-Shock Proteins; D006046:Gold
Gold nanorods (AuNRs); Heat shock protein 70 (HSP70); Plasmonic photothermal therapy (PPTT); Protein refolding; Quercetin (QE)