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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.

Objective: To prepare the Gd-DTPA-loaded poly (lactic-co-glycolic acid) (PLGA) microbubbles for both ultrasound imaging and MRI imaging., Methods: Biodegradable high-molecular-weight poly (lactic-co-glycolic acid) (PLGA) was used as an encapsulating vehicle to fabricate a contrast agent composed of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) and fluorocarbon-filled microbubbles by using double emulsion method. The morphology, size, and Gd loading capacity of PLGA microparticles were assessed. The efficacy of the contrast agent for ultrasound and magnetic resonance (MR) imaging was evaluated by in vivo imaging of hepatic vessels and the liver parenchyma of rabbit following injection of the contrast agent. Additionally, the liver and kidney functions were examined before and at 7, 14, 30 days after injection., Results: Electron microscopy showed Gd loaded PLGA microbubbles were spherical in shape. The mean diameter were 1.47 +/- 0.38 microm and the Gd loading was 25 +/- 2 microg/mg. Right after the injection of the PLGA microbubbles, the ultrasound echo intensity of hepatic vessels and the liver parenchyma was significantly enhanced. Moreover, enhanced signal intensity of the liver parenchyma on MR images was observed for approximately 30 min after injection of the contrast agent. Neither marked changes in the liver and kidney functions nor other severe complications were detected during the follow-up period., Conclusion: Gd-DTPA-loaded PLGA microbubbles could enhance both ultrasound imaging and MRI imaging., ((c) 2010 Wiley Periodicals, Inc.)

Background: Recent studies have demonstrated that multidrug resistance (MDR) is a critical factor in the low efficacy of cancer chemotherapy. The main mechanism of MDR arises from the overexpression of P-glycoprotein (P-gp), which actively enhances drug efflux and limits the effectiveness of chemotherapeutic agents. Results: In this study, we fabricated a "combo" nanoagent equipping with triple synergistic strategies for enhancing antitumor efficacy against MDR cells. Tumor homing-penetrating peptide endows the nanosystem with targeting and penetrating capabilities in the first stage of tumor internalization. The abundant amine groups of polyethylenimine (PEI)-modified nanoparticles then trigger a proton sponge effect to promote endo/lysosomal escape, which enhances the intracellular accumulation and retention of anticancer drugs. Furthermore, copper tetrakis(4-carboxyphenyl)porphyrin (CuTCPP) encapsulated in the nanosystem, effectively scavenges endogenous glutathione (GSH) to reduce the detoxification mediated by GSH and sensitize the cancer cells to drugs, while simultaneously serving as a photoacoustic imaging (PAI) contrast agent for image visualization. Moreover, we also verify that these versatile nanoparticles in combination with PD-1/PD-L1 blockade therapy can not only activate immunological responses but also inhibit P-gp expression to obliterate primary and metastatic tumors. Conclusion: This work shows a significant enhancement in therapeutic efficacy against MDR cells and syngeneic tumors by using multiple MDR reversing strategies compared to an equivalent dose of free paclitaxel. [ABSTRACT FROM AUTHOR]