Novel ultrasound-responsive chitosan/perfluorohexane nanodroplets for image-guided smart delivery of an anticancer agent: Curcumin

• Novel chitosan/PFH nanodroplets were synthesized for smart curcumin delivery.
• US-aided curcumin release synergized with US enhanced targeted delivery of curcumin.
• US contrast effect of nanodroplets was approved by b-mode US imaging.
• Sonication significantly enhanced cytotoxicity of curcumin-loaded nanodroplets.
• Chitosan/PFH nanodroplets could be promising agents for image guided chemotherapy.

Ultrasound-responsive nanodroplets are a class of new emerging smart drug delivery systems which provide image-guided nano-therapy of various diseases, especially cancers. Here, we developed multifunctional smart curcumin-loaded chitosan/perfluorohexane nanodroplets for contrast-ultrasound imaging and on-demand drug delivery. The nanodroplets were synthesized via nanoemulsion process. The optimal formulation with the size of 101.2 nm and 77.8% curcumin entrapment was chosen for release study and cytotoxicity evaluation. Sonication at the frequency of 1 MHz, 2 W/cm2 for 4 min triggered the release of 63.5% of curcumin from optimal formulation (Cur-NDs-2). Ultrasound aided release study indicated that the concentration of perfluorohexane and the degree of acoustic droplet vaporization play important role in ultrasound-active drug release. B-mode ultrasound imaging confirmed strong ultrasound contrast of chitosan nanodroplets even at low concentrations via droplet to bubble transition. Finally, cytotoxicity of the ultrasound-responsive nanodroplets in the presence of ultrasound was evaluated in-vitro on 4T1 human breast cancer cells. Cell growth inhibitory effects of curcumin-loaded nanodroplets significantly increased by ultrasound exposure. According to the obtained results, these ultrasound responsive curcumin-loaded chitosan/perfluorohexane nanodroplets have a great potential for imaged-guided cancer therapy.