Preparation of Microbubble Contrast Material of Sulfhydryl-Maleimide Group and Its Application in Ultrasound Diagnosis of Breast Cancer

In this study, an ultrasound microbubble contrast agent with integrin αvβ3 as the target was prepared. It was used for the target-finding diagnosis of breast cancer cells. The sulfhydryl group of iRGD peptide and the maleimide group of DSPE-PEG2000 Maleimides were connected by a thin-film hydration method to obtain a new type of ultrasound microbubble contrast agent (iRGD-DSM). First, a particle size analyzer and an optical microscope were used to characterize the iRGD-DSM. Then, the mouse breast cancer cell 4T1 was used for breast cancer ultrasound diagnosis by in vitro culture, and the binding of the contrast agent to the cells was analyzed. Also, quantitative analysis was performed by flow cytometry. The test results showed that an iRGD peptide, iRGD/DSPE-P2000, was obtained based on the chemical coupling of sulfhydryl-maleimide groups. In terms of average particle size, microbubble distribution, and concentration, the iRGD-DSM contrast agent prepared in this study was similar to conventional microbubble contrast agents. Also, when the DSPC, DSPEPEG, iRGD/DSPE-P2000 molar ratio is 36:3:1, higher peptide content can be obtained. Dynamic/static specific targeting of vascular endothelial cells (bEND.3) adhesion test confirmed that iRGD-DSM contrast agent can be firmly combined with bEND.3. In the target-finding test of breast cancer cells 4T1, the ultrasound microbubble contrast agent proposed based on this study had obvious binding imaging with breast cancer cells 4T1. In numerical analysis, the binding rate of the contrast agent to 4T1 cells reached (95.75 ± 1.43)%. Therefore, it was confirmed that the ultrasound microbubble contrast agent iRGD-DSM with integrin αvβ3 as a target has certain in vitro targeting ability for breast cancer diagnosis.

Ultrasound microbubble contrast agent – carried chemotherapeutic drug microbubbles

With the continuous research and development of ultrasound microbubble contrast agent-carried chemotherapeutic drug microbubbles, ultrasound microbubble contrast agent not only facilitates the early detection and early diagnosis of tumors but also provides a new direction and development prospect for the drug delivery route. With a broad development prospect, it is expected to become a new safe, effective and non-invasive treatment. This paper reviews the biological effects and research progress of contrast-enhanced microbubble-loaded chemotherapy drugs in tumor therapy.

Opening the Blood-Brain Barrier and Improving the Efficacy of Temozolomide Treatments of Glioblastoma Using Pulsed, Focused Ultrasound with a Microbubble Contrast Agent

Objective.To explore the effects of pulsed, focused, and microbubble contrast agent-enhanced ultrasonography (mCEUS) on blood-brain barrier (BBB) permeability and the efficacy temozolomide for glioblastoma.Methods.Wistar rats (n = 30) were divided into three groups (n = 10 per group) to determine optimal CUES conditions for achieving BBB permeability, as assessed by ultrastructure transmission electron microscopy (TEM) and western blot assays for the tight junction protein claudin-5. Optimized mCEUS effects on BBB permeability were subsequently confirmed with Evans blue staining (2 groups of 10 rats). The glioma cell line 9L was injected into the brain striatum of Wistar rats. After temozolomide chemotherapy, we detected glial fibrillary acidic protein (GFAP) levels in serum by enzyme-linked immunosorbent assay (ELISA) and in brain tissue by western blot, immunocytochemistry, and real-time quantitative polymerase chain reaction (qPCR).Results.BBB permeability was maximized with 1 ml/kg contrast agent mCEUS delivered via 10-min intermittent launches with a 400-ms interval. Evans blue staining confirmed BBB permeability following ultrasonic cavitation in the control group (P < 0.05). Following temozolomide chemotherapy, levels of the tumor marker GFAP were increased in the group with ultrasonic cavitation compared with the control group (P < 0.05).Conclusions.When rats were treated by mCEUS with intermittent launches (interval, 400 ms) and injected with 1 mg/kg contrast agent, BBB permeability was increased and temozolomide BBB penetration was enhanced, therapeutic enhancement for glioblastoma.