Among medical imaging modalities available in the clinic, ultrasonography is the most convenient, inexpensive, ionizing-radiation-free, and most common. Micrometer-size perfluorocarbon bubbles have been used as efficient contrast for intravascular ultrasonography, but they are too big for tumor penetration. Nanodroplets (250-1000 nm) encapsulating both perfluorocarbon and drug have been used as an ultrasound-triggered release drug delivery platform against cancer, but they are generally not useful as a tumor imaging agent. The present study aims to develop a type of pH-sensitive, polymersome-based, perfluorocarbon encapsulated ultrasonographic nanoprobe, capable of maintaining at 178 nm during circulation and increasing to 437 nm at the acidic tumor microenvironment. Its small size allowed efficient tumor uptake. At the tumor site, the nanoparticle swells, resulting in lowering of the vaporization threshold for the perfluorocarbon, efficient conversion of nanoprobes to echogenic nano/microbubbles for ultrasonic imaging, and eventual release of doxorubicin from the theranostic nanoprobe for deep tissue chemotherapy, triggered by irradiation with low-frequency ultrasound.
Keywords: deep tissue chemotherapy; fluorescence/ultrasound imaging; pH-/thermosensitivity; perfluorocarbon; size regulation; theranostics; ultrasonographic nanoprobe.