Hematoporphyrin encapsulated PLGA microbubble for contrast enhanced ultrasound imaging and sonodynamic therapy

The purpose of this study was to develop a sonosensitizer-loaded multi-functional ultrasound (US) contrast agent for both tumour therapy and imaging. The hematoporphyrin (HP)-encapsulated poly(lactic-co-glycolic acid) microbubbles (HP-PLGA-MBs) were prepared and filled with perfluorocarbon gases. The enhancement of US imaging and its sonodynamically induced anti-tumour effect were evaluated by both in vitro and in vivo experiments. The HP-PLGA-MBs have a narrow size distribution and smooth surface with a mean diameter of 702.6 ± 56.8 nm and HP encapsulation efficiency of 63.50 ± 1.26% and drug-loading efficiency of 2.15 ± 0.13%. The HP-PLGA-MBs could well enhance the ultrasound imaging both in vitro and in vivo. A significant anti-tumour effect was obtained by HP-PLGA-MBs mediated sonodynamic therapy. The tumour growth rate and the tumour proliferation index were the lowest in the HP-PLGA-MBs plus sonication group. And the tumour cell apoptotic index was the biggest in the HP-PLGA-MBs plus sonication group. In conclusion, a sonosensitizer-loaded multi-functional contrast agent was constructed and the feasibility was demonstrated, which might provide a novel strategy for tumour imaging and therapy.