A Lipopeptide-Based αvβ3 Integrin-Targeted Ultrasound Contrast Agent for Molecular Imaging of Tumor Angiogenesis

Yan, Fei; Xu, Xiu-xia; Chen, Yihan; Deng, Zhiting; Li, Hongmei; Xu, Jing; Zhou, Jie; Tan, Guangming; Wu, Junru; Zheng, Hairong

doi:10.1016/j.ultrasmedbio.2015.05.023

Cited by 33 publications

(24 citation statements)

References 31 publications

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“…TMUCA would improve diagnostic specificity and allow for disease monitoring in real time. TMUCAs can accumulate and remain at the tumor site for long time periods, and imaging at the molecular level can be acquired using US after TMUCA venous injection [1–3]. US molecular imaging also produces quantitative data, exhibits good temporal resolution, is noninvasive, produces no ionizing radiation, and is relatively inexpensive [4].…”

Section: Introductionmentioning

confidence: 99%

Rituximab-conjugated, doxorubicin-loaded microbubbles as a theranostic modality in B-cell lymphoma

2016

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This study evaluated rituximab-conjugated, doxorubicin-loaded microbubbles (RDMs) in combination with ultrasound as molecular imaging agents for early diagnosis of B cell lymphomas, and as a targeted drug delivery system. Rituximab, a monoclonal CD20 antibody, was attached to the surfaces of doxorubicin-loaded microbubbles. RDM binding to B cell lymphoma cells was assessed using immunofluorescence. The cytotoxic effects of RDMs in combination with ultrasound (RDMs+US) were evaluated in vitro in CD20+ and CD20-cell lines, and its antitumor activities were assessed in Raji (CD20+) and Jurkat (CD20-) lymphoma cell-grafted mice. RDMs specifically bound to CD20+ cells in vitro and in vivo. Contrast enhancement was monitored in vivo via ultrasound. RDM peak intensities and contrast enhancement durations were higher in Raji than in Jurkat cell-grafted mice (P<0.05). RDMs+US treatment resulted in improved antitumor effects and reduced systemic toxicity in Raji cell-grafted mice compared with other treatments (P<0.05). Our results showed that RDMs+US enhanced tumor targeting, reduced systemic toxicity, and inhibited CD20+ B cell lymphoma growth in vivo. Targeted RDMs could be employed as ultrasound molecular imaging agents for early diagnosis, and are an effective targeted drug delivery system in combination with ultrasound for CD20+ B cell malignancy treatment.

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Section: Introductionmentioning

confidence: 99%

Rituximab-conjugated, doxorubicin-loaded microbubbles as a theranostic modality in B-cell lymphoma

2016

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“…Due to their small size, nanobubbles has greater potential in targeted molecular imaging and therapeutic application than that of microsized UCAs [17, 29, 30]. For example, NBs can efficiently penetrate through submucosal layers for tumor imaging [31, 32] and have longer circulation times in vivo [18, 19, 33]. The goal of this work was to investigate the characteristics of the novel silicon-modified nanobubbles as ultrasound contrast agents for the ultrasound imaging in vivo.…”

Section: Discussionmentioning

confidence: 99%

Preparation and characterization of a novel silicon-modified nanobubble

Liu

Zhang

et al. 2017

PLoS ONE

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Nanobubbles (NBs) opened a new field of ultrasound imaging. There is still no practical method to control the diameter of bubbles. In this study, we developed a new method to control the size by incorporating of silicon hybrid lipids into the bubble membrane. The range of particle size of resulting NBs is between 523.02 ± 46.45 to 857.18 ± 82.90, smaller than the conventional microbubbles. The size of resulting NBs increased with the decrease in amount of silicon hybrid lipids, indicating the diameter of NBs can be regulated through modulating the ratio of silicon hybrid lipids in the bubble shell. Typical harmonic signals could be detected. The in vitro and in vivo ultrasound imaging experiments demonstrated these silicon-modified NBs had significantly improved ultrasound contrast enhancement abilities. Cytotoxicity assays revealed that these NBs had no obvious cytotoxicity to the 293 cell line at the tested bubble concentration. Our results showed that the novel NBs could use as nanoscale ultrasound contrast agents, providing the foundation for NBs in future applications including contrast-enhanced imaging and drug/gene delivery.

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“…Several integrins are involved in cancer progression but most of them, such as αvβ3, are over expressed, making them difficult to quantify [6,11,12]. We successfully evaluated colocalization using Imaris (Bit plane Scientific Software) to quantify the percentage of colocalization between the 2 CD31 and β3 markers, and found that colocalized β3/CD31 areas made up 30.6% of the vasculature area.…”

Section: Immunofluorescencementioning

confidence: 99%