Perfluorohexane-cored nanodroplets for stimulations-responsive ultrasonography and O2-potentiated photodynamic therapy

To achieve efficient ultrasonography-guided photodynamic therapy (PDT), two major obstacles need to be overcome. On the one hand, O2-dependent PDT produces limited effects on hypoxic solid tumors. On the other hand, small particles facilitate tumor accumulation whereas large ones strengthen ultrasound (US) imaging, which makes the development of an ultrasonographic probe showing effective tumor accumulation and high US sensitivity an intractable challenge. Therefore, an intelligent perfluorohexane (PFH)-based nanodroplet, PFH@Ce6@O2, was fabricated in order to simultaneously solve the above problems. The nanoscale PFH@Ce6@O2 particles were firstly delivered to elevate the local O2 level of tumors, which is critical for achieving excellent PDT effect under laser irradiation. Then, a spontaneous “small-to-large” growth of droplet at tumor acidic microenvironment resulted in an echo-contrast enhancement for high-performance US imaging of tumor. The in vitro and in vivo results manifested the advantage of PFH@Ce6@O2 in alleviating hypoxic status to inhibit tumor growth. Overall, PFH@Ce6@O2 integrating US/FL bimodal imaging and PDT effect appears to be a promising nanoplatform for ultrasonography-guided PDT of solid tumors.