Radio frequency triggered curcumin delivery from thermo and pH responsive nanoparticles containing gold nanoparticles and its in vivo localization studies in an orthotopic breast tumor model
Non-invasive radiofrequency (RF) electric fields as an energy source for thermal activation of nanoparticles and thereby delivering drugs within cancer cells could be a valuable addition to nano-mediated RF based cancer therapies. Utilizing the high penetration of RF waves would be useful for the controlled release of encapsulated drug molecules from smart thermo and pH responsive nanoparticles. Herein, we demonstrate that breast cancer cells could selectively internalize hemocompatible, 170 ± 20 nm sized curcumin encapsulated chitosan-graft-poly(N-vinyl caprolactam) nanoparticles containing gold nanoparticles (Au-CRC-TRC-NPs). Au-CRC-TRC-NPs were predominantly accumulated within the cytoplasm. After “optimum RF exposure” at 40 watts for 5 minutes, Au-CRC-TRC-NPs absorbed and dissipated energy as heat in the range of 42 °C, which is the lower critical solution temperature (LCST) of chitosan-graft-poly(N-vinyl caprolactam), causing controlled curcumin release and inducing apoptosis to 4T1 breast cancer cells. Further, the tumor localization studies on orthotopic breast cancer models revealed that Au-CRC-TRC-NPs could selectively accumulate at primary and secondary tumors as confirmed by in vivo live imaging followed by ex vivo tissue imaging and HPLC studies. These preclinical results throw light on their feasibility as a better tumor targetable nanomedicine for RF-assisted breast treatment modalities.