Surface-crosslinked multi-functional nanodroplets for photoacoustic/ultrasound image-guided high intensity focused ultrasound therapy

We have developed surface-crosslinked polymer nanodroplets having capabilities of therapeutic enhancement for high intensity focused ultrasound (HIFU) treatment and image guidance by photoacoustic (PA) and ultrasound (US) imaging. Six-arm-branched poly(ethylene glycol) (PEG) is crosslinked with Pluronic F127 mixed with naphthalocyanine (Nc), and sonicated with liquid perfluorohexane (PFH) to form nanoparticles encapsulating Nc and PFH (Nc/PFH@PCPN). The Nc dye provides high optical absorption at 850 nm wavelength for PA imaging, and improves the stability of the nanodroplets due to its hydrophobicity. PFH evaporates upon reception of HIFU waves to form microbubbles that enhances both visual contrast for US imaging and cavitation effect for HIFU treatment. We have shown from experiments that the nanodroplets significantly increase the signal contrast of the PA/US images, and at the same time they enhance the HIFU cavitation effect and induce necrosis and apoptosis of tumor cells. Thus, we believe Nc/PFH@PCPN can be a biocompatible and stable multi-functional agent for HIFU therapy guided by PA/US images.1