Breast Cancers: MR Imaging of Folate-Receptor Expression with the Folate-Specific Nanoparticle P1133

Meier, Reinhard; Henning, Tobias D.; Boddington, Sophie; Tavri, Sidhartha; Arora, Sandeep; Piontek, Guido; Rudelius, Martina; Corot, Claire; Daldrup-Link, Heike E.

doi:10.1148/radiol.10090050

Cited by 127 publications

(100 citation statements)

References 31 publications

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“…Based on these observations, we next determined whether CT20p-mediated detachment of MDA-MB-231 cells was accompanied by alterations in integrins that are aberrantly expressed in breast cancer. 24, 25, 26, 27 Cells were treated with CT20p, and α 5 and α V integrins were detected by immunoblot (Figure 5c), whereas β 1 and β 3 integrins were assessed by flow cytometry (Figure 5d). In MDA-MB-231, but not MCF-10A cells, β 1 decreased after 3 h of CT20p treatment, whereas surface levels of β 3 were not altered until after 24 h (Figure 5d).…”

Section: Resultsmentioning

confidence: 99%

“…Two different HBPE-NPs were used for delivery of CT20p: untargeted carboxylated (COOH) nanoparticles (used in in vitro experiments) and folate-decorated (FOL) nanoparticles that target cells expressing folate receptors, like MDA-MB-231 cells. 27 From our previous studies, we knew that untargeted and folate-targeted nanoparticles were equally effective in vitro ; however, we anticipated that the folate-targeted nanoparticles would concentrate more effectively in tumors when introduced intravenously. Further, to improve circulation and prevent uptake by the reticuloendothelial system, nanoparticles were pegylated, which did not impair uptake by cells as shown using nanoparticles loaded with a dye (Supplementary Figure 4A).…”

Section: Resultsmentioning

confidence: 99%

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The CT20 peptide causes detachment and death of metastatic breast cancer cells by promoting mitochondrial aggregation and cytoskeletal disruption

et al. 2014

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Metastasis accounts for most deaths from breast cancer, driving the need for new therapeutics that can impede disease progression. Rationally designed peptides that take advantage of cancer-specific differences in cellular physiology are an emerging technology that offer promise as a treatment for metastatic breast cancer. We developed CT20p, a hydrophobic peptide based on the C terminus of Bax that exhibits similarities with antimicrobial peptides, and previously reported that CT20p has unique cytotoxic actions independent of full-length Bax. In this study, we identified the intracellular actions of CT20p which precede cancer cell-specific detachment and death. Previously, we found that CT20p migrated in the heavy membrane fractions of cancer cell lysates. Here, using MDA-MB-231 breast cancer cells, we demonstrated that CT20p localizes to the mitochondria, leading to fusion-like aggregation and mitochondrial membrane hyperpolarization. As a result, the distribution and movement of mitochondria in CT20p-treated MDA-MB-231 cells was markedly impaired, particularly in cell protrusions. In contrast, CT20p did not associate with the mitochondria of normal breast epithelial MCF-10A cells, causing little change in the mitochondrial membrane potential, morphology or localization. In MDA-MB-231 cells, CT20p triggered cell detachment that was preceded by decreased levels of α5β1 integrins and reduced F-actin polymerization. Using folate-targeted nanoparticles to encapsulate and deliver CT20p to murine tumors, we achieved significant tumor regression within days of peptide treatment. These results suggest that CT20p has application in the treatment of metastatic disease as a cancer-specific therapeutic peptide that perturbs mitochondrial morphology and movement ultimately culminating in disruption of the actin cytoskeleton, cell detachment, and loss of cell viability.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The CT20 peptide causes detachment and death of metastatic breast cancer cells by promoting mitochondrial aggregation and cytoskeletal disruption

et al. 2014

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“…The two breast cancer cell lines analyzed in this study were MDA-MB-231 and MCF-7, both of which express folate receptor, although MDA-MB-231 cells express FR-α to a greater extent than MCF-7 cells [34, 35]. Recent efforts to quantify folate receptor isoform expression on the surface of breast cancer cells has shown that MDA-MB-231 cells have 1.76 times more FR-α expression relative to MCF-7 cells [35].…”

Section: Introductionmentioning

confidence: 99%

Intracellular delivery and ultrasonic activation of folate receptor-targeted phase-change contrast agents in breast cancer cells in vitro

Marshalek

Sheeran

Ingram

et al. 2016

Journal of Controlled Release

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Breast cancer is a diverse and complex disease that remains one of the leading causes of death among women. Novel, outside-of-the-box imaging and treatment methods are needed to supplement currently available technologies. In this study, we present evidence for the intracellular delivery and ultrasound-stimulated activation of folate receptor (FR)-targeted phase-change contrast agents (PCCAs) in MDA-MB-231 and MCF-7 breast cancer cells in vitro. PCCAs are lipid-coated, perfluorocarbon-filled particles formulated as nanoscale liquid droplets capable of vaporization into gaseous microbubbles for imaging or therapy. Cells were incubated with 1:1 decafluorobutane (DFB) / octafluoropropane (OFP) PCCAs for 1 hour, imaged via confocal microscopy, exposed to ultrasound (9 MHz, MI = 1.0 or 1.5), and imaged again after insonation. FR-targeted PCCAs were observed intracellularly in both cell lines, but uptake was significantly greater (p < 0.001) in MDA-MB-231 cells (93.0% internalization at MI = 1.0, 79.5% at MI = 1.5) than MCF-7 cells (42.4% internalization at MI = 1.0, 35.7% at MI = 1.5). Folate incorporation increased the frequency of intracellular PCCA detection 45-fold for MDA-MB-231 cells and 7-fold for MCF-7 cells, relative to untargeted PCCAs. Intracellularly activated PCCAs ranged from 500 nm to 6 microns (IQR = 800 nm – 1.5 microns) with a mean diameter of 1.15 ± 0.59 (SD) microns. The work presented herein demonstrates the feasibility of PCCA intracellular delivery and activation using breast cancer cells, illuminating a new platform toward intracellular imaging or therapeutic delivery with ultrasound.

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“…Confirmation of MRI signal intensification via this method was performed by near infrared fluorescent imaging of the targeting peptides labeled with near infrared dye [18]. Other strategies for enhanced MRI signals have included the use of folate receptor targeted magnetic oxide nanoparticles [19]. Gold nanoshells Antibody to HER2 NIR fluorescent imaging in vitro In vitro PT [84] LHRH, leutenizing hormone releasing hormone; PT, photothermal; N/A, not applicable.…”

Section: Targeting Of Nanoparticles For Delivery To Metastatic Breastmentioning

confidence: 99%

Nanoparticle delivery for metastatic breast cancer

Grobmyer¹,

Zhou²,

Gutwein³

et al. 2012

Maturitas

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Breast cancer represents a major ongoing public health problem as the most common non-cutaneous malignancy among U.S. women. While significant progress has been made in improving loco-regional treatments for breast cancer, relatively little progress has been made in diagnosing and treating patients with metastatic breast cancer. At present there are limited curative options for patients with breast cancer metastatic beyond regional nodes. Emerging nanotechnologies promise new approaches to early detection and treatment of metastatic breast cancer. Fulfilling the promise of nanotechnologies for patients with metastatic breast cancer will require delivery of nanomaterials to sites of metastatic disease. Future translational approaches will rely on an ever increasing understanding of the biology of breast cancer subtypes and their metastases. These important concepts will be highlighted and elucidated in this manuscript.

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Breast Cancers: MR Imaging of Folate-Receptor Expression with the Folate-Specific Nanoparticle P1133

Abstract: The FR-targeted USPIO P1133 demonstrates a specific retention in FR-positive breast cancers. Because FR expression correlates with tumor aggressiveness and prognosis, persistent P1133 tumor enhancement may be used as a noninvasive indicator for tumors with poor outcome.

Cited by 127 publications

References 31 publications

The CT20 peptide causes detachment and death of metastatic breast cancer cells by promoting mitochondrial aggregation and cytoskeletal disruption

The CT20 peptide causes detachment and death of metastatic breast cancer cells by promoting mitochondrial aggregation and cytoskeletal disruption

Intracellular delivery and ultrasonic activation of folate receptor-targeted phase-change contrast agents in breast cancer cells in vitro

Nanoparticle delivery for metastatic breast cancer

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