Nanoparticles carrying paclitaxel and anti-miR-221 for breast cancer therapy triggered by ultrasound.

Nanomaterials have been well demonstrated to have the potential to be used for tumor cell-targeted drug delivery. Targeted inhibition of miR-221 was proved to promote the sensitivity of triple genitive breast cancer (TNBC) cells to chemo-drugs. In order to improve the chemotherapeutic effect in TNBC, herein, we developed a novel kind of nanoparticles shelled with PLGA and loaded with perfluoropentane (PFP), paclitaxel (PTX), and anti-miR-221 inhibitor, which was named PANP. Ultrasound-triggered vaporization of PFP in PANPs was utilized for real-time imaging track of the nanoparticles in vivo. In addition, macrophages were applied for the internalization of PANPs to form RAW-PANP with strong chemotaxis to accumulate around cancer cells. Nanoparticles with different contents did not cause M2 polarization compared with the control group but caused polarization toward M1. We compared the inherent tumor-homing behavior of macrophages containing different contents with that of normal macrophages and no significant abnormalities were observed. After injection into the tumor-burden mice, RAW-PANPs showed enrichment within tumor tissues. Upon the ultrasound cavitation-triggered burst, PTX was released in the tumor. Meanwhile, the release of anti-miR-221 improved the sensitivity of tumor cells to PTX. As a result, RAW-PANPs showed high efficiency in suppressing TNBC cell proliferation in vitro and inhibiting tumor growth and progression in vivo. The treatments did not induce liver, heart, or kidney injury. In conclusion, the current study not only developed a macrophage-carried, ultrasound-triggered, cancer cell-targeted chemotherapeutic system, but also demonstrated a miRNA-based technique to promote drug sensitivity of cancer cells, which holds strong potential to treat patients with TNBC, especially for those suffering drug-resistance. The innovation of this study is to use macrophages to deliver nanoparticles to the tumors and then use ultrasound locally to burst the nanoparticles to release the miRNA and PTX.

Ultrasound monitoring of magnet-guided delivery of mesenchymal stem cells labeled with magnetic lipid-polymer hybrid nanobubbles.

Restenosis remains a pressing clinical problem that occurs in patients undergoing revascularization procedures, such as coronary artery bypass surgery and percutaneous transluminal angioplasty. Previous reports have proved that mesenchymal stem cells (MSCs) could effectively reduce the restenosis resulting from intimal hyperplasia following vascular injury. However, non-invasive delivery of MSCs and real-time monitoring of their retention at the site of vascular injury still remain a significant challenge. Therefore, we synthesized magnetic lipid-polymer hybrid nanobubbles (Mag-LPNs) as ultrasound contrast agents for cellular labeling of MSCs, endowing these MSCs with magnetic responsibility and real-time tracking capability by ultrasound. In order to enhance the internalization efficiency of MSCs, Mag-LPNs were modified with cationic polymers to generate positively charged Mag-LPNs (P-Mag-LPNs). Intriguingly, the internalization of P-Mag-LPNs did not exhibit obvious harmful effects on the labeled MSCs in terms of cell viability and differentiation capacity. Moreover, the magnet-guided delivery of labeled MSCs in a rat carotid artery injury model developed using a 2-French balloon catheter could be tracked by ultrasound in a real-time manner. About 5-fold more MSCs were attached at the site of the injured artery with the aid of an external magnet field, compared with the absence of a magnet field. Herein, our study provides an innovative tracking platform for magnet-guided delivery of stem cells treating cardiovascular diseases.

The Role of Blood Flow in Corpus Luteum Measured by Transvaginal Two-Dimensional and Three-Dimensional Ultrasound in the Prediction of Early Intrauterine Pregnancy Outcomes.

Objective: The purpose of this study was to explore the application of transvaginal two-dimensional and three-dimensional power Doppler ultrasound in pregnancy corpus luteum to predict the final outcome of early intrauterine pregnancy. Methods: This is a prospective observational cohort study. Six hundred early intrauterine pregnant women in Shanghai Changning Maternity and Infant Health Hospital were selected as the research objects from January 2015 to December 2015. According to the follow-up of 12 weeks, these pregnant women were divided into the normal pregnancy group (group A, n = 512) and the terminational pregnancy group (group B, n = 88). They all underwent both transvaginal two-dimensional ultrasound and three-dimensional power Doppler ultrasound to obtain relevant parameters of corpus luteum, namely, the average diameter of the corpus luteum (D), resistance index (RI), pulsatility index (PI), corpus luteum volume (V), vascularization index (VI), blood flow index (FI), and vascularized blood flow index (VFI). Among them, V, VI, FI, and VFI were calculated with the virtual organ computer-aided analysis method. Receiver operator characteristic (ROC) curves were drawn. The corresponding diagnostic cut-off, sensitivity, and specificity were calculated and compared. Results: Compared with group A, the D, V, VI, FI, and VFI of corpus luteum in group B were statistically significant lower while RI and PI were statistically significant higher (P < 0.05). The diagnostic cut-off values in the prediction of early intrauterine pregnancy outcomes were D: 14.48, RI: 0.56, PI: 0.81, V: 3.89, VI: 21.48, FI: 38.99, and VFI: 10.21 respectively, and the sensitivity and specificity were D (99.2%, 67.0%), RI (98.9%, 65.0%), PI (78.4%, 89.1%), V (95.1%, 78.4%), VI (74.%, 90.9%), FI (91.8%, 90.9%), and VFI (93.9%, 87.5%) respectively. The area under the ROC curve of the combined index (RI + FI) was 0.963, which was not significantly higher compared with any single index, and both the sensitivity and specificity were 94.3%. Conclusion: Both transvaginal two-dimensional and three-dimensional ultrasonography are of high diagnostic value in predicting the early intrauterine pregnancy outcomes.

Molecular Ultrasound Monitoring of Early Artery Injury After Carotid Balloon Angioplasty.

Cardiovascular intervention is a common treatment procedure for many cardiovascular diseases. But restenosis often occurs after these procedures, greatly discounting their long-term therapeutic effects. Early detection of endothelial denudation is helpful for the diagnosis and prevention of restenosis. Here, we fabricated targeted microbubbles by conjugating anti-collagen IV antibodies to the surface of biotinylated microbubbles (MBColIV) and applied them for ultrasound molecular imaging of endothelial injury at early stage. Our results showed that the MBColIV, with a typical multi-peak particle distribution, was successfully constructed, which was confirmed by Alexa Fluor® 555-labeled secondary antibody. Ex vivo adhesion of microbubbles revealed that MBColIV can effectively and specially bind to the surface of balloon-injured carotid artery. The in vivo animal experiments showed ultrasound molecular imaging signals from carotid artery-injured rats administrated with MBColIV were significantly higher than those administrated with isotype control microbubbles. Histological staining of the left carotid common artery revealed that collagen IV was obviously exposed after endothelium denudation in balloon-injured artery. In conclusion, our current study provides an effective approach to detect vascular injury at the early stage and a potential platform for image-guided therapy to vascular injury.