期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 42, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.nano.2022.102533
关键词
Nanobubbles; Molecular ultrasound imaging; EPR effect; Legumain; RGD
资金
- National Natural Science Foundation of China [81502297, 81270774, 81871487]
In this study, we synthesized nanobubbles with a small size and modified their surface with peptides targeting tumor cells and tumor neovasculature. The dual targeted nanobubbles showed efficient and specific imaging of breast cancer in both in vitro and in vivo experiments, demonstrating their potential for cancer diagnosis and monitoring.
Molecular ultrasound imaging is a promising strategy for non-invasive and precise cancer diagnosis. Previously reported ultrasound contrast agents (UCAs) are mostly microbubbles or nanobubbles (NBs) larger than 200 nm, leading to less efficient tumor delivery. Here we synthesized NBs with a small size (similar to 49 nm) and modified the NB surface with alanine-alanine-asparagine (NB-A) or arginine-glycine-aspartic acid peptide (NB-R) for concurrent active targeting towards legumain in tumor cells and integrin in tumor neovasculature. In vitro, the NB-A and NB-R presented echogenicity comparable with SonoVue MBs and showed specific binding with tumors cells and endothelial cells, respectively. In vivo, the combined NB-A/NB-R accumulated in tumor tissues selectively and provided ultrasound signals with prolonged duration and that were significantly stronger than non-targeted NBs, single-targeted NBs and SonoVue MBs. Overall, the dual targeted NBs served as efficient UCAs for specific imaging of breast cancer, and hold great potential for general cancer diagnosis/monitoring in the future. (C) 2022 Elsevier Inc. All rights reserved.
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