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

Author(s):  
Jing-Jing Liu ◽  
Zun Wang ◽  
Li-Ming Nie ◽  
Yuan-Yuan Zhu ◽  
Ge Li ◽  
...  

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.

Author(s):  
Jing-Jing Liu ◽  
Zun Wang ◽  
Li-Ming Nie ◽  
Yuan-Yuan Zhu ◽  
Ge Li ◽  
...  

Abstract Purpose Obtaining tumour-free margins is critical for avoiding re-excision and reducing local recurrence following breast-conserving surgery; however, it remains challenging. Imaging-guided surgery provides precise detection of residual lesions and assists surgical resection. Herein, we described water-soluble melanin nanoparticles (MNPs) conjugated with cyclic Arg-Gly-Asp (cRGD) peptides for breast cancer photoacoustic imaging (PAI) and surgical navigation. Methods The cRGD-MNPs were synthesised and characterized for morphology, photoacoustic characteristics and stability. Tumour targeting and toxicity of cRGD-MNPs were determined by using either breast cancer cells, MDA-MB-231 tumour-bearing mice or the FVB/N-Tg (MMTV-PyVT) 634Mul/J mice model. PAI was used to locate the tumour and guide surgical resection in MDA-MB-231 tumour-bearing mice. Results The cRGD-MNPs exhibited excellent in vitro and in vivo tumour targeting with low toxicity. Intravenous administration of cRGD-MNPs to MDA-MB-231 tumour-bearing mice showed an approximately 2.1-fold enhancement in photoacoustic (PA) intensity at 2 h, and the ratio of the PA intensity at the tumour site to that in the surrounding normal tissue was 3.2 ± 0.1, which was higher than that using MNPs (1.7 ± 0.3). Similarly, the PA signal in the spontaneous breast cancer increased ~ 2.5-fold at 2 h post-injection of cRGD-MNPs in MMTV-PyVT transgenic mice. Preoperative PAI assessed tumour volume and offered three-dimensional (3D) reconstruction images for accurate surgical planning. Surgical resection following real-time PAI showed high consistency with histopathological analysis. Conclusion These results highlight that cRGD-MNP-mediated PAI provide a powerful tool for breast cancer imaging and precise tumour resection. cRGD-MNPs with fine PA properties have great potential for clinical translation.


2020 ◽  
Vol 8 (4) ◽  
pp. 261 ◽  
Author(s):  
Claudio Luparello ◽  
Debora Ragona ◽  
Dalia Maria Lucia Asaro ◽  
Valentina Lazzara ◽  
Federica Affranchi ◽  
...  

Triple-negative breast cancer (TNBC) is a highly malignant tumor histotype which lacks effective targeted therapies, thereby being considered as the most aggressive form of breast carcinoma. To identify novel compounds which could counteract TNBC cell growth, we explored the in vitro effects of crude extracts and <10 kDa-filtered fractions of the coelomic fluid obtained from the sea urchin Arbacia lixula on TNBC MDA-MB231 cells. We examined cell viability, cycle distribution, apoptotic/autophagic activity, and mitochondrial polarization/cell redox status. Here, we report the first data demonstrating an anti-TNBC effect by A. lixula-derived coelomic fluid extracts. Thus, identification of the water-soluble bioactive component(s) contained in the extracts deserve(s) further investigation aimed to devise novel promising prevention and/or treatment agents effective against highly malignant breast tumors.


RSC Advances ◽  
2016 ◽  
Vol 6 (69) ◽  
pp. 64306-64314 ◽  
Author(s):  
M. H. Han ◽  
Z. T. Li ◽  
D. D. Bi ◽  
Y. F. Guo ◽  
H. X. Kuang ◽  
...  

Cholesterol-PEG1000-FA (folic acid) was synthesized as a stabilizer to encapsulate DTX, for the construction of a promising targeted delivery system for breast cancer therapy.


2020 ◽  
Vol 12 (7) ◽  
pp. 1099-1108
Author(s):  
Siqin Li ◽  
Huicheng Lv

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.


NANO ◽  
2014 ◽  
Vol 09 (07) ◽  
pp. 1450073 ◽  
Author(s):  
XING REN ◽  
HAILONG HUANG ◽  
JINGYUAN WANG ◽  
GUANG SUN ◽  
ZHELI XU

This research is aimed to develop a novel kind of biomarker based on water-soluble quantum dots (QDs) conjugated with estrogen receptor (ER) for the detection of breast cancer (BC). To achieve the purpose, hydrophobic octadecylamine-coated QDs were encapsulated with amphiphilic biocompatible centipede-like polymer p(aspartate)- Na -graft-p(ethylene glycol)-dodecylamine (PASP- Na -g-PEG-DDA), and then modified with ER monoclonal antibodies, which is one of the most popular biomarkers for the detection and management of breast cancer worldwide. The targeted QDs kept the original optical property of QDs. The cytotoxicity in vitro experiments showed that QDs-ER probes had no obvious toxic side effects. Remarkably, confocal laser scanning microscopy (CLSM) revealed that the localized fluorescence appeared around the nucleus of human breast cancer cell MCF7 (ER positive) compared with that of human breast cancer cell MBA-MD-231 (ER negative). According to the above analysis, this new kind of probe has great potential in the diagnosis of breast tumor in vitro in future clinical application.


The Breast ◽  
1999 ◽  
Vol 8 (2) ◽  
pp. 84-88 ◽  
Author(s):  
M. Douek ◽  
T. Davidson ◽  
M.A. Hall-Craggs ◽  
S.R. Lakhani ◽  
M. Baum ◽  
...  

2015 ◽  
Vol 9 (1) ◽  
pp. 29-35
Author(s):  
Sherif Abdelhamid ◽  
Ahmed Talha ◽  
Salwa Hamdy ◽  
Ashraf Arafat Abdelhalim ◽  
Mohamed Elakany

Background: This study was purposed to compare in vitro the volumetric accuracy of a newly introduced automatic infusion controller, AutoClamp with that of other commonly used infusion devices. Methods: In this prospective, randomized, controlled trial, 124 ASA I-II, female patients, aged 30-50 years, undergoing conservative breast cancer surgery were randomly assigned to one of four equal groups receiving either standard general anesthesia and two doses of hydrocortisone (Group GH, n=31), thoracic paravertebral block and two doses of hydrocortisone (Group PH, n=31), standard general anesthesia with no hydrocortisone (Group G, n=31), or thoracic paravertebral block with no hydrocortisone (Group P, n=31). IL-6 was measured at three time points: before operation, 6 and 12 hours postoperatively. CRP and cortisol were measured preoperatively and 6 hours postoperatively. Results: On comparing group PH and GH, there was significant decrease in IL-6 level in group PH compared to group GH at 6 hour (122.1±21.2 vs 135.8±29.8pg/dl), but insignificant difference at 24 hours (107.9±21.6 vs 106.8±15.9pg/dl). CRP showed significant decrease in the postoperative reading in group PH compared to group GH (1.63±0.32 vs 1.91±0.43mg/l), and also group PH showed significant decrease compared to the control group P (1.63±0.32 vs 2.2±0.54). Conclusion: addition of hydrocortisone to general anesthesia or thoracic paravertebral block attenuated production of IL-6 and CRP levels significantly postoperatively compared to either anesthetic regimen alone, but not the serum cortisol level, highlighting its role in modifying the stress response to surgery. However, the effect was more pronounced when combined with thoracic paravertebral block.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Pengcheng Xu ◽  
Ru Wang ◽  
Wenqian Yang ◽  
Yanyan Liu ◽  
Dongsheng He ◽  
...  

Abstract Background Although many treatments for breast cancer are available, poor tumour targeting limits the effectiveness of most approaches. Consequently, it is difficult to achieve satisfactory results with monotherapies. The lack of accurate diagnostic and monitoring methods also limit the benefits of cancer treatment. The aim of this study was to design a nanocarrier comprising porous gold nanoshells (PGNSs) co-decorated with methoxy polyethylene glycol (mPEG) and trastuzumab (Herceptin®, HER), a therapeutic monoclonal antibody that binds specifically to human epidermal receptor-2 (HER2)-overexpressing breast cancer cells. Furthermore, a derivative of the microtubule-targeting drug maytansine (DM1) was incorporated in the PGNSs. Methods Prepared PGNSs were coated with mPEG, DM1 and HER via electrostatic interactions and Au–S bonds to yield DM1-mPEG/HER-PGNSs. SK-BR-3 (high HER2 expression) and MCF-7 (low HER2) breast cancer cells were treated with DM1-mPEG/HER-PGNSs, and cytotoxicity was evaluated in terms of cell viability and apoptosis. The selective uptake of the coated PGNSs by cancer cells and subsequent intracellular accumulation were studied in vitro and in vivo using inductively coupled plasma mass spectrometry and fluorescence imaging. The multimodal imaging feasibility and synergistic chemo-photothermal therapeutic efficacy of the DM1-mPEG/HER-PGNSs were investigated in breast cancer tumour-bearing mice. The molecular mechanisms associated with the anti-tumour therapeutic use of the nanoparticles were also elucidated. Result The prepared DM1-mPEG/HER-PGNSs had a size of 78.6 nm and displayed excellent colloidal stability, photothermal conversion ability and redox-sensitive drug release. These DM1-mPEG/HER-PGNSs were taken up selectively by cancer cells in vitro and accumulated at tumour sites in vivo. Moreover, the DM1-mPEG/HER-PGNSs enhanced the performance of multimodal computed tomography (CT), photoacoustic (PA) and photothermal (PT) imaging and enabled chemo-thermal combination therapy. The therapeutic mechanism involved the induction of tumour cell apoptosis via the activation of tubulin, caspase-3 and the heat shock protein 70 pathway. M2 macrophage suppression and anti-metastatic functions were also observed. Conclusion The prepared DM1-mPEG/HER-PGNSs enabled nanodart-like tumour targeting, visibility by CT, PA and PT imaging in vivo and powerful tumour inhibition mediated by chemo-thermal combination therapy in vivo. In summary, these unique gold nanocarriers appear to have good potential as theranostic nanoagents that can serve both as a probe for enhanced multimodal imaging and as a novel targeted anti-tumour drug delivery system to achieve precision nanomedicine for cancers.


2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Ekaterina I. Galanzha ◽  
Robert Weingold ◽  
Dmitry A. Nedosekin ◽  
Mustafa Sarimollaoglu ◽  
Jacqueline Nolan ◽  
...  

Abstract Understanding cell biology greatly benefits from the development of advanced diagnostic probes. Here we introduce a 22-nm spaser (plasmonic nanolaser) with the ability to serve as a super-bright, water-soluble, biocompatible probe capable of generating stimulated emission directly inside living cells and animal tissues. We have demonstrated a lasing regime associated with the formation of a dynamic vapour nanobubble around the spaser that leads to giant spasing with emission intensity and spectral width >100 times brighter and 30-fold narrower, respectively, than for quantum dots. The absorption losses in the spaser enhance its multifunctionality, allowing for nanobubble-amplified photothermal and photoacoustic imaging and therapy. Furthermore, the silica spaser surface has been covalently functionalized with folic acid for molecular targeting of cancer cells. All these properties make a nanobubble spaser a promising multimodal, super-contrast, ultrafast cellular probe with a single-pulse nanosecond excitation for a variety of in vitro and in vivo biomedical applications.


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