Preparation and Imaging Investigation of Dual-targeted C3F8-filled PLGA Nanobubbles as a Novel Ultrasound Contrast Agent for Breast Cancer

ABSTRACTA new type of difolate targeting nano-level ultrasound contrast agent ((folate molecule, FOL)2-TUAs) was prepared, so as to investigate its targeted binding effect with human breast cancer mammary carcinoma cells (MCF-7) in vitro. L-2-aminoadipic acid (L-2-AD) as a branch unit was inserted at the hydroxyl end of distearoyl phosphatidylethanolamine (DISP)-PEG2000-COOH to construct a tree structure. At this time, the free hydroxyl group in the distearoyl phosphatidylethanolamine (DISP)-PEG2000-COOH structure modified the FOL with the help of N-Hydroxysuccinimide/N,N'-dicyclohexylcarbodiimide (NHS/DCC). Each 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DISP-PEG2000) connected two FOLs to generate difolate targeted nanomaterials. Nano laser particle size (PS) and Zeta potential analyzer (ZPA) were applied to analyze the physical characteristics of the material such as PS and dispersion, and the enhanced development effect in vitro was detected by the ultrasonic diagnostic instrument. Besides, the targeted binding ability of the contrast agent based on this material to folate receptor (FR) overexpressing MCF-7 cells was analyzed by flow cytometry (FCM) and fluorescence microscope. In the experiment, hydrogen-1 nuclear magnetic resonance (1H NMR) demonstrated that (FOL)2-TUAs was successfully synthesized. The surface of this material was round and uniformly distributed without aggregation. According to the relative number of FOL molecules, non-targeted nano-agent (U-TUA), monofolate targeted nano-agent (FOL-TUA), and difolate targeted nano-agent ((FOL)2-TUA) were obtained. The in vitro imaging showed that different materials exhibited enhanced imaging effects in ultrasonic diagnostic equipment. FCM and fluorescence microscopy both indicated that the difolate TUA could achieve a good binding to MCF-7 cells. Most of the nano-agents were attached to the cell membrane, surrounded by red fluorophore, namely increasing the FOL content of DISP-PEG2000 chain could enhance the targeted binding ability of tumor cells.

Download Full-text

Ultrasound molecular imaging of breast cancer in MCF-7 orthotopic mice using gold nanoshelled poly(lactic-co-glycolic acid) nanocapsules: a novel dual-targeted ultrasound contrast agent

International Journal of Nanomedicine ◽

10.2147/ijn.s153993 ◽

2018 ◽

Vol Volume 13 ◽

pp. 1791-1807 ◽

Cited By ~ 8

Author(s):

Li Xu ◽

Jing Du ◽

Caifeng Wan ◽

Yu Zhang ◽

Shaowei Xie ◽

...

Keyword(s):

Breast Cancer ◽

Molecular Imaging ◽

Contrast Agent ◽

Glycolic Acid ◽

Ultrasound Contrast Agent ◽

Ultrasound Contrast ◽

Targeted Ultrasound ◽

Ultrasound Molecular Imaging ◽

Mcf 7

Download Full-text

Mesoporous silica nanoparticles as a breast-cancer targeting ultrasound contrast agent

Colloids and Surfaces B Biointerfaces ◽

10.1016/j.colsurfb.2013.10.038 ◽

2014 ◽

Vol 116 ◽

pp. 652-657 ◽

Cited By ~ 72

Author(s):

Andrew Milgroom ◽

Miranda Intrator ◽

Krishna Madhavan ◽

Luciano Mazzaro ◽

Robin Shandas ◽

...

Keyword(s):

Breast Cancer ◽

Mesoporous Silica ◽

Contrast Agent ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Ultrasound Contrast Agent ◽

Cancer Targeting ◽

Ultrasound Contrast

Download Full-text

Preparation of anti-HER-2 antibody PLGA polymer nano- ultrasound contrast agent In vitro targeting experiment

10.1101/619742 ◽

2019 ◽

Author(s):

Ji Lin ◽

Molly Stevens ◽

John Smith

Keyword(s):

Breast Cancer ◽

Particle Size ◽

Electron Microscope ◽

Contrast Agent ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Ultrasound Contrast Agent ◽

Ultrasound Contrast ◽

Her 2

AbstractIn this report, we demonstrated a novel method to prepare a hollow nano-targeted ultrasound contrast agent carrying anti-HER-2 antibody with high molecular weight polylactic acid-glycolic acid (PLGA) as a film-forming material, and to investigate in vitro targeting and imaging effects. We utilized the camphor as porogen, PLGA nano-ultrasound contrast agent was prepared by modified double emulsion solvent evaporation method. The general characteristics were characterized by scanning electron microscope, transmission electron microscope and laser particle size analyzer. The angiography was performed by carbodiimide method. The anti-HER-2 antibody was used to prepare the PLGA-targeted nano-ultrasound contrast agent with anti-HER-2 antibody. The in-situ imaging ability was evaluated by laser confocal scanning microscopy. Results indicate that the average particle size of PLGA nano-ultrasound contrast agent was (152.00± 58.08) nm. The particles were regular spherical, uniform in size and good in dispersion. In vitro targeting experiments showed that PLGA-targeted contrast agents with anti-HER-2 antibodies were more strongly aggregated on the surface of breast cancer cells. In vitro imaging experiments showed that the PLGA-targeted nano-ultrasound contrast imaging showed a fine and uniform point-like hyperechoic echo, and no significant attenuation of the posterior echo. This study successfully produced a PLGA-targeted nano-ultrasound contrast agent with anti-HER-2 antibody, which can specifically bind to breast cancer cells with high expression of HER-2 receptor in vitro, and the imaging effect in vitro is better.

Download Full-text