Preparation of Lipid Nanovesicle Contrast Material and Its Application in Ultrasound Diagnosis of Breast Cancer Tumor

2020 ◽  
Vol 12 (7) ◽  
pp. 1099-1108
Author(s):  
Siqin Li ◽  
Huicheng Lv
Keyword(s):  
Breast Cancer ◽  
Contrast Agent ◽  
Light Absorption ◽  
Photoacoustic Imaging ◽  
Contrast Material ◽  
Ultrasound Diagnosis ◽  
Strong Light ◽  
Good Imaging ◽  
Significant Difference

In this study, a kind of melanin lipid nanovesicle contrast agent (M-lvca) material with good light absorption and melanin doping is proposed. In this contrast material, lipid nanospheres containing melanin are obtained by ether titration. Then, it is prepared by freeze-drying. In the experimental part, the shape, structure, particle size and absorption spectrum of the material are studied. In vitro agarose gel model, the ultrasound/photoacoustic analysis of the contrast agent is carried out to detect the effect of different concentration of contrast agent on phagocytosis of cells. In the diagnosis of breast cancer, the enhancement boundary, the distribution of contrast agent, the enhancement shape, the range change after enhancement, and the penetration of blood vessels are detected. The experimental results show that the contrast agent has the characteristics of microsphere shape, uniform distribution and strong light absorption ability in the wavelength range of 100 nm∼900 nm. In vitro ultrasound imaging/photoacoustic imaging test, the contrast agent has a good imaging ability. With the increase of the concentration, the imaging ability will be further enhanced. In the diagnosis of breast cancer, there is a significant difference in the indexes related to ultrasound diagnosis of breast cancer after adding M-lvca contrast agent (P < 0.05). Only a few indexes such as enhancement intensity and perfusion defect have no significant difference (P > 0.05). In this study, the proposed M-lvca material can improve the imaging effect of related indicators in the early diagnosis of breast cancer, which is helpful to improve the accuracy of breast cancer diagnosis.

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

2020 ◽  
Vol 12 (9) ◽  
pp. 1361-1370
Author(s):  
Juan Liu ◽  
Wenbin Zhu ◽  
Hongyan Chen ◽  
Ying Lin ◽  
Xueqin Li
Keyword(s):  
Breast Cancer ◽  
Particle Size ◽  
Contrast Agent ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Ultrasound Diagnosis ◽  
Average Particle ◽  
Microbubble Contrast Agent ◽  
Maleimide Group

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.

Novel Difolate Targeting Nano-Level Ultrasound Contrast Agent for Therapy of Breast Cancer Tumor Cells

2021 ◽  
Vol 13 (7) ◽  
pp. 1295-1303
Author(s):  
Guangheng Liu ◽  
Xiangfeng Yang ◽  
Qiming Niu ◽  
Wenkui Sun
Keyword(s):  
Breast Cancer ◽  
Contrast Agent ◽  
Tumor Cells ◽  
Folate Receptor ◽  
Ultrasound Contrast Agent ◽  
Hydroxyl Group ◽  
Binding Ability ◽  
Ultrasound Contrast ◽  
Mcf 7

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.

scholarly journals Asialoglycoprotein Receptor-Targeted Superparamagnetic Perfluorooctylbromide Nanoparticles

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Yang Li ◽  
Chao Feng Yang ◽  
Hui Zuo ◽  
Ao Li ◽  
Sushant Kumar Das ◽  
...  
Keyword(s):  
Contrast Agent ◽  
Rat Liver ◽  
Liver Parenchyma ◽  
Asialoglycoprotein Receptor ◽  
Enhancement Effect ◽  
Receptor Imaging ◽  
Significant Difference ◽  
Mean Size

Background. The decrease in asialoglycoprotein receptor (ASGPR) levels is observed in patients with chronic liver disease and liver tumor. The aim of our study was to develop ASGPR-targeted superparamagnetic perfluorooctylbromide nanoparticles (M-PFONP) and wonder whether this composite agent could target buffalo rat liver (BRL) cells in vitro and could improve R2 ∗ value of the rat liver parenchyma after its injection in vivo. Methods. GalPLL, a ligand of ASGPR, was synthesized by reductive amination. ASGPR-targeted M-PFOBNP was prepared by a film hydration method coupled with sonication. Several analytical methods were used to investigate the characterization and safety of the contrast agent in vitro. The in vivo MR T2 ∗ mapping was performed to evaluate the enhancement effect in rat liver. Results. The optimum concentration of Fe3O4 nanoparticles inclusion in GalPLL/M-PFOBNP was about 52.79 µg/mL, and the mean size was 285.6 ± 4.6 nm. The specificity of GalPLL/M-PFOBNP for ASGPR was confirmed by incubation experiment with fluorescence microscopy. The methyl thiazolyl tetrazolium (MTT) test showed that there was no significant difference in the optical density (OD) of cells incubated with all GalPLL/M-PFOBNP concentrations. Compared with M-PFOBNP, the increase in R2 ∗ value of the rat liver parenchyma after GalPLL/M-PFOBNP injection was higher. Conclusions. GalPLL/M-PFOBNP may potentially serve as a liver-targeted contrast agent for MR receptor imaging.

Contrast-enhanced ultrasound (CEUS) in assessing early response among patients with invasive breast cancer undergoing neoadjuvant chemotherapy

2016 ◽  
Vol 58 (4) ◽  
pp. 394-402 ◽  
Author(s):  
Ariel Saracco ◽  
Botond K Szabó ◽  
Ervin Tánczos ◽  
Jonas Bergh ◽  
Thomas Hatschek
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Contrast Agent ◽  
Real Time ◽  
Invasive Breast Cancer ◽  
Early Response ◽  
Contrast Enhanced Ultrasound ◽  
Time Harmonic ◽  
Contrast Enhanced ◽  
Significant Difference

Background One of the big challenges in onco-radiology is to find a reliable imaging method that may predict early response during the first cycles of any neoadjuvant chemotherapy. Purpose To evaluate the use of real-time harmonic contrast-enhanced ultrasound (CEUS) in predicting early response in breast cancer tumors under neoadjuvant chemotherapy (NAC) treatment. Material and Methods Nineteen consecutive patients with invasive breast cancer were evaluated with a bolus dose of 2.4 mL contrast agent using CEUS, before and after two cycles of epirubicin and docetaxel. The lognormal function was used for quantitative analysis of kinetic data to evaluate early response. Results There was statistically significant difference in time-to-peak ( tp) between responders and non-responders (two sample t-test, P = 0.027) where tp was significantly longer at the week 5 than at the baseline scan among responders when compared to non-responders. Conclusion In-flow of intravascular contrast agent in tumors is significantly slower in responders at real-time harmonic CEUS, and might be effectively used for the evaluation of early response to chemotherapy in invasive breast cancer. However, further investigations in a larger and more heterogeneous population should be performed to corroborate the reliability of the method.

scholarly journals Photoacoustic Properties of Polypyrrole Nanoparticles

Nanomaterials ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2457
Author(s):  
Peter Keša ◽  
Monika Paúrová ◽  
Michal Babič ◽  
Tomáš Heizer ◽  
Petr Matouš ◽  
...  
Keyword(s):  
Contrast Agent ◽  
Photoacoustic Imaging ◽  
Particle Surface ◽  
Photoacoustic Signal ◽  
Ammonium Persulphate ◽  
Coated Nanoparticles ◽  
Polypyrrole Nanoparticles ◽  
Signal Dependence

Photoacoustic imaging, an emerging modality, provides supplemental information to ultrasound imaging. We investigated the properties of polypyrrole nanoparticles, which considerably enhance contrast in photoacoustic images, in relation to the synthesis procedure and to their size. We prepared polypyrrole nanoparticles by water-based redox precipitation polymerization in the presence of ammonium persulphate (ratio nPy:nOxi 1:0.5, 1:1, 1:2, 1:3, 1:5) or iron(III) chloride (nPy:nOxi 1:2.3) acting as an oxidant. To stabilize growing nanoparticles, non-ionic polyvinylpyrrolidone was used. The nanoparticles were characterized and tested as a photoacoustic contrast agent in vitro on an imaging platform combining ultrasound and photoacoustic imaging. High photoacoustic signals were obtained with lower ratios of the oxidant (nPy:nAPS ≥ 1:2), which corresponded to higher number of conjugated bonds in the polymer. The increasing portion of oxidized structures probably shifted the absorption spectra towards shorter wavelengths. A strong photoacoustic signal dependence on the nanoparticle size was revealed; the signal linearly increased with particle surface. Coated nanoparticles were also tested in vivo on a mouse model. To conclude, polypyrrole nanoparticles represent a promising contrast agent for photoacoustic imaging. Variations in the preparation result in varying photoacoustic properties related to their structure and allow to optimize the nanoparticles for in vivo imaging.

Quinidine as a resistance modulator of epirubicin in advanced breast cancer: mature results of a placebo-controlled randomized trial.

1994 ◽  
Vol 12 (9) ◽  
pp. 1771-1777 ◽  
Author(s):  
G C Wishart ◽  
D Bissett ◽  
J Paul ◽  
D Jodrell ◽  
A Harnett ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Response Rate ◽  
Advanced Breast ◽  
Toxicity Profile ◽  
Survival Times ◽  
Double Blind ◽  
P Glycoprotein ◽  
Significant Difference

PURPOSE To evaluate the effect of quinidine, a putative modulator of P-glycoprotein-mediated drug resistance, on the response rate and toxicity profile of epirubicin in patients with advanced breast cancer. PATIENTS AND METHODS Between 1989 and 1992, 223 eligible patients were randomized in double-blind fashion to receive epirubicin 100 mg/m2 by intravenous (i.v.) bolus and prednisolone 25 mg orally twice daily, along with either placebo or quinidine (250 mg) capsules, taken for 4 days before and 2 days after chemotherapy. Treatment was continued for a maximum of eight courses. RESULTS Ten eligible patients did not complete the first cycle of treatment. Of the remaining patients, 106 in the placebo arm received 619 courses of treatment, and 107 in the quinidine arm received 612 courses. The median cumulative dose of epirubicin in both arms was 600 mg/m2. The median quinidine level (measured before epirubicin administration in 288 courses) was 5.5 mumol/L; at this concentration, the drug partially reverses anthracycline resistance in multidrug-resistant (MDR) breast carcinoma cells in vitro. There were no statistically significant differences in hematologic or gastrointestinal toxicity between the two arms. The response rate in the placebo arm was 44% (6% complete remission [CR], 38% partial remission [PR]), and in the quinidine arm was 43% (4% CR, 39% PR). Surviving patients have been monitored for a median time of 74 weeks, and there is no significant difference in the overall or progression-free survival between the two arms. The median survival times were 59 weeks for placebo and 47 weeks for quinidine patients. The estimated relative death rate (quinidine/placebo) was 1.2 (P = .247; 95% confidence interval [CI], 0.88 to 1.63). CONCLUSION Quinidine at this dose does not significantly alter the toxicity profile, response rate, or survival after epirubicin chemotherapy in patients with advanced breast cancer. This may be due to ineffective modulation of P-glycoprotein by quinidine or the lack of expression of mdr-1 in a sufficient proportion of cells in these tumors, or alternative mechanisms underlying resistance to epirubicin.

scholarly journals RGD-Functionalized Melanin Nanoparticles for Intraoperative Photoacoustic Imaging-Guided Breast Cancer Surgery

2021 ◽  
Author(s):  
Jing-Jing Liu ◽  
Zun Wang ◽  
Li-Ming Nie ◽  
Yuan-Yuan Zhu ◽  
Ge Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Surgical Resection ◽  
Photoacoustic Imaging ◽  
Water Soluble ◽  
Breast Cancer Surgery ◽  
Tumour Resection ◽  
Histopathological Analysis ◽  
Tumour Targeting ◽  
Tumour Bearing

Abstract Purpose: Obtaining tumour-free margins is critical for avoiding re-excision and 35 reducing local recurrence following breast-conserving surgery (BCS); however, it 36 remains challenging. Imaging-guided surgery provides precise detection of residual 37 lesions and assists surgical resection. Herein, we describe water-soluble melanin 38 nanoparticles (MNPs) conjugated with cyclic Arg-Gly-Asp (cRGD) peptides for breast 39 cancer photoacoustic imaging (PAI) and surgery navigation. 40Methods: cRGD-MNPs was synthesized and characterized for morphology, 41 photoacoustic characteristics and stability. Tumour targeting and toxicity were 42 determined by cells and tumour-bearing mice. PAI was used to locate the tumour and 43 guide surgical resection in MDA-MB-231 tumour-bearing mice. 44Results: The cRGD-MNPs exhibited excellent tumour-targeting in vitro and in vivo, 45 with low toxicity. Intravenous administration of cRGD-MNPs to MDA-MB-231 46 tumour-bearing mice showed an approximately 2.1-fold enhancement in photoacoustic 47 (PA) intensity at 2 h, and the ratio of the PA intensity at the tumour site compared to 48 that in the surrounding normal tissue was 3.2 ± 0.1, which was much higher than that 49 using MNPs alone (1.7 ± 0.3). Similarly, the PA signal in the mammary glands 50 containing spontaneous breast cancer was enhanced (2.5 ± 0.3-fold) in MMTV-PyVT 51 transgenic murine model. Preoperative screening by PAI could assess tumour volume 52 and offer a three-dimensional (3D) reconstruction image for accurate surgical planning. 53 Surgical resection following real-time PAI on the tumour bed showed high consistency 54 with histopathological analysis. 55Conclusion: These results highlight that cRGD-MNPs combined with PAI provide 56 a powerful tool for breast cancer imaging and precise tumour resection. cRGD-MNPs 57 with good PA properties have great potential for clinical translation.

Phase III Study of N,N-Diethyl-2-[4-(Phenylmethyl) Phenoxy]Ethanamine (BMS-217380-01) Combined With Doxorubicin Versus Doxorubicin Alone in Metastatic/Recurrent Breast Cancer: National Cancer Institute of Canada Clinical Trials Group Study MA.19

2004 ◽  
Vol 22 (2) ◽  
pp. 269-276 ◽  
Author(s):  
Leonard Reyno ◽  
Lesley Seymour ◽  
Dongsheng Tu ◽  
Susan Dent ◽  
Karen Gelmon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Recurrent Breast Cancer ◽  
Phase Iii ◽  
Metastatic Breast Carcinoma ◽  
Significant Difference ◽  
Recurrent Breast

Purpose N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine (DPPE; tesmilifene) is a novel agent that augments chemotherapy cytotoxicity in vitro and in vivo. A phase II trial combining DPPE and doxorubicin (DOX) in metastatic breast carcinoma showed increased response over that expected with DOX. We report a phase III trial comparing DOX with DPPE plus DOX in metastatic or recurrent breast cancer. Patients and Methods Anthracycline-naive women with measurable metastatic disease were randomly assigned to receive, every 21 days, either DOX 60 mg/m2 intravenously or DOX during the last 20 minutes of an 80-minute infusion of DPPE (5.3 mg/kg), in both cases to cumulative DOX doses of 450 mg/m2. Patients receiving DPPE were aggressively premedicated to ameliorate toxicity. End points included progression-free survival (PFS), response rate (RR), and response duration (RD), quality of life (QOL), toxicity, and overall survival (OS). Results A planned interim analysis failed to detect an RR difference more than 5%. The study was closed to additional accrual and all DPPE was discontinued. The final analysis was conducted as planned after 256 progression events (median follow-up, 20.5 months). There was no significant difference in RR, RD, or PFS between arms. DPPE plus DOX was statistically superior to DOX in OS (hazard ratio, 0.66; 95% CI, 0.48 to 0.91; P = .021). DPPE plus DOX was associated with more gastrointestinal and CNS toxicity. No consistent influence on QOL was detected. Conclusion This study demonstrated no advantage in RR, RD, or PFS but significantly superior OS for DPPE plus DOX. Additional studies of DPPE are warranted.

scholarly journals Propofol Reduced Mammosphere Formation of Breast Cancer Stem Cells via PD-L1/Nanog In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaobei Zhang ◽  
Fangxuan Li ◽  
Ying Zheng ◽  
Xiaokun Wang ◽  
Kaiyuan Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cell Proliferation ◽  
Cancer Stem Cells ◽  
Cancer Recurrence ◽  
Tumor Formation ◽  
Breast Cancer Stem Cells ◽  
Mammosphere Formation ◽  
Significant Difference

Several researches revealed that propofol, a hypnotic intravenous anesthesia agent, could inhibit the cancer cell proliferation and tumor formation, which might affect cancer recurrence or metastasis and impact patients’ prognosis. Cancer stem cells (CSCs) comprised a tiny fraction of tumor bulk and played a vital role in cancer recurrence and eventual mortality. This study investigates the effect of propofol on breast cancer stem cells (BCSCs) in vitro and the underlying molecular mechanisms. Tumor formation of CSCs was measured by mammosphere culture. Cultured BCSCs were exposed to different concentrations and durations of propofol. Cell proliferation and self-renewal capacity were determined by MTT assays. Expressions of PD-L1 and Nanog were measured using western blotting and real-time PCR. We knocked down the PD-L1 expression in MDA-MB-231 cells by lentivirus-mediated RNAi technique, and the mammosphere-forming ability of shControl and shPD-L1 under propofol treatment was examined. Mammosphere culture could enrich BCSCs. Compared with control, cells exposed to propofol for 24 h induced a larger number of mammosphere cells (P=0.0072). Levels of PD-L1 and Nanog were downregulated by propofol. Compared with shControl stem cells, there was no significant difference in the inhibitory effect of propofol on the mammosphere-forming ability of shPD-L1 stem cells which indicated that the inhibition of propofol could disappear in PD-L1 knockdown breast stem cells. Propofol could reduce the mammosphere-forming ability of BCSCs in vitro. Mechanism experiments indicated that the inhibition of propofol in mammosphere formation of BCSCs might be mediated through PD-L1, which was important to maintain Nanog.

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