Atherosclerosis is a major cause of sudden death and myocardial infarction, instigated by unstable plaques. Thus, the early detection of unstable plaques and corresponding treatment can improve the prognosis and reduce mortality. In this study, we describe a protocol for the preparation of nanoparticles (NPs) combined with the phase transitional material perfluorohexane (PFH) and with dextran sulfate (DS) targeting class A scavenger receptors (SR-A) for the diagnosis and treatment of atherosclerotic vulnerable plaques. The results showed that the Fe-PFH-poly(lactic-co-glycolic acid) (PLGA)/chitosan (CS)-DS NPs were fabricated successfully, with the ability to undergo phase transition by low-intensity focused ultrasound (LIFU) irradiation to achieve ultrasound imaging; a high carrier rate of Fe 3 O 4 had a good negative enhancement effect on magnetic resonance imaging (MRI). The NPs had a high binding affinity for activated macrophages and could be endocytosed by the macrophages and notably induced apoptosis under LIFU irradiation by an acoustic droplet vaporization effect in vitro. Furthermore, in an ex vivo atherosclerotic plaque model of apolipoprotein E knockout (KO) (apoE −/− ) mice induced by high cholesterol, the NPs selectively accumulated at the sites of SR-A expressed on the activated macrophages of the aortic region. This result was also confirmed by MRI in vivo, where the NPs could be targeted to the aortic plaque and reduced the T 2 * signal. The LIFU-induced phase transition could lead to the apoptosis of macrophages on plaques in vivo. In summary, Fe-PFH-PLGA/CS-DS NPs may be applied as multimodal and multifunctional probes and are expected to enable the specific diagnosis and targeted therapy of vulnerable plaques.

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Sonodynamic therapy (SDT) is a highly promising approach for cancer therapy, but its efficacy is severely hampered by the low specificity of sonosensitizers and the unfavorable characteristics of the tumor...

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Background: Some patients with cervical cancer have the need to preserve fertility; therefore, a minimally invasive treatment option that can effectively inactivate tumors in these patients is necessary. Methods: In this paper, we designed and prepared nanoparticles (NPs) carrying IR780 and perfluorohexane (PFH) and characterized their properties. We focused on the promotion of programmed low-intensity focused ultrasound (LIFU) irradiation on the penetration and treatment of cervical cancer. First we used penetration-enhancing LIFU irradiation to promote the penetration of the NPs into 3D multicellular tumor spheroids (MCTSs) and tumors in tumor-bearing nude mice. Then we used re-therapeutic LIFU irradiation to achieve antitumor effects in vitro and in vivo. Photoacoustic (PA) and magnetic resonance (MR) imaging were used to monitor and evaluate the targeting and therapeutic effects of these NPs on tumor tissues. Results:The NPs prepared in this paper exhibited high affinity for HeLa cells, and can selectively achieve mitochondrial localization in the cell due to IR780 assistance. The penetration-enhancing LIFU irradiation have the ability to promote the penetration of the NPs into cervical cancer models in vivo and in vitro. Under LIFU irradiation, the cytotoxic reactive oxygen species (ROS) produced by IR780 during the first half of the re-therapeutic LIFU irradiation and the physical acoustic droplet vaporization (ADV) effect after PFH phase transition during the second half of the re-therapeutic LIFU irradiation can achieve synergistic minimally invasive treatment of tumors, which can be visualized and evaluated by PA and MR imaging in vivo. Conclusion:Well-programmed LIFU irradiation can promote NP penetration into deep tumor tissue and achieve antitumor effects simultaneously. Linking ROS + ADV effects can induce cell coagulation necrosis and lead to a comprehensive, long-term impact on tumor tissue, providing a conceptual theranostic nanoplatform for cervical cancer.