Selective Uptake of a Fructose Glycopolymer Prepared by RAFT Polymerization into Human Breast Cancer Cells

Ehe, Christian von der; Rinkenauer, Alexandra C.; Weber, C.; Szamosvári, Dávid; Gottschaldt, Michael; Schubert, Ulrich S.

doi:10.1002/mabi.201500346

Cited by 30 publications

(53 citation statements)

References 29 publications

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“…HEA‐micelles and fructose‐micelles were exposed to these cell lines for 2 h using similar polymer concentration. The fluorescence intensity of each type of micelles was normalized[20b] according to values obtained from fluorospectrometry prior to the flow cytometry test. This was necessary as the encapsulation efficiency of Nile Red differed between the two micelles (Tables S1 and S2, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

“…In this paper, we demonstrate how the use of fructose‐decorated nanoparticles can enhance the favorable properties further. Glycopolymer with pendant fructose groups were shown to display an enhanced cellular uptake by cancerous cells . Polymers based on fructose were found to be more efficient than other glycopolymers in their ability to enhance cellular uptake .…”

Section: Introductionmentioning

confidence: 99%

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Enhanced Antimetastatic Activity of the Ruthenium Anticancer Drug RAPTA‐C Delivered in Fructose‐Coated Micelles

Chen

Noy

et al. 2017

Macromolecular Bioscience

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(HER-2) has been utilized as a targeting site for the Trastuzumab drug delivery system. Trastuzumab is a humanized monoclonal antibody and has been widely used for HER2-positive metastatic breast cancer. [2] In the case of triplenegative breast cancer, [3] which is lacking the expression of progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor 2 (HER-2/neu), other targeting mechanism are sought after. Interestingly, an overexpression of fructose transporter GLUT5 could be observed in cell lines such as MCF-7 and MDA-MB-231. [4] Glucose transporters (GLUTs) are transmembrane proteins, which participate in the cellular uptake of carbohydrates in order to provide energy for cellular metabolism. [5] This possible targeting mechanism has been investigated by Zhang et al. who have successfully applied fructose pendants on phosphorescent metal complexes to increase the cellular uptakes of the complexes. [6] The ruthenium complex-dichlororuthenium (II) (p-cymene) (1,3,5-triaza-7-phosphaadamantane) (RAPTA-C)-has shown to be remarkably effective at suppressing the growth of solid tumor metastases. However, poor delivery efficacy and the lack of targeting ability of the common drug delivery system pose significant obstacles to maximize the therapeutic benefit of RAPTA-C. Inspired by the overexpression of GLUT5 transporter on the surface of breast cancer tissues but not the healthy mammary tissues, the use of d-fructose as the targeting moiety of the drug carrier can significantly improve the cellular uptake of nanoparticles, thus further enhancing the therapeutic efficiency of RAPTA-C. In this work, fructose-micelles and 2-hydroxyethyl acrylate (HEA)-micelles are prepared to investigate the difference in cellular uptake. It is found that glycopolymer leads to an increased uptake by breast cancer cells, while the HEA-micelles show less uptake. This behavior is also reflected by the slightly faster movement of fructose-coated micelles in MCF-7 tumor spheroid models using light sheet microscopy as analytical tool. The incorporation of RAPTA-C into micelles can enhance the inhibitory effect of the ruthenium drug demonstrated using invasion, chemotaxis, and haptotaxis assays. As a result, fructose-coated nanoparticles can be a promising drug delivery platform of RAPTA-C for the treatment of metastatic breast cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enhanced Antimetastatic Activity of the Ruthenium Anticancer Drug RAPTA‐C Delivered in Fructose‐Coated Micelles

Chen

Noy

et al. 2017

Macromolecular Bioscience

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“…However SEC measurements in eluent blends including alcohols have only been reported rarely [16], [17] and there appears to be only one recent report on the use of methanol or ethanol as the sole component of the eluent, in an ultra high pressure SEC system [1]. In some instances preventing adsorption involves modifying organic eluents [18], [19], [20] or using buffered aqueous media [21], [22]. In our experience, the analysis of polyacrylamides often requires changing the eluent if pendant or chain-end functionalities are modified.…”

Section: Introductionmentioning

confidence: 99%

Analysis using size exclusion chromatography of poly( N -isopropyl acrylamide) using methanol as an eluent

Swift

Hoskins

Telford

et al. 2017

Journal of Chromatography A

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“…23,25 Specifically, nanoparticles prepared from fructose-based glycopolymers were found to be promising nano-carriers for triple-negative breast cancer therapy. [26][27][28] These micelles normally exhibit excellent 4 breast cancer cell-specific uptake and their internalization is heavily dependent on nanoparticle size and attachment site of fructose moieties. Initially, thorough investigations have been carried out to determine the parameters that influence the aspect ratio of the rod-like micelles.…”

mentioning

confidence: 99%

Cellular Uptake and Movement in 2D and 3D Multicellular Breast Cancer Models of Fructose-Based Cylindrical Micelles That Is Dependent on the Rod Length

Zhao

Xiao

et al. 2016

ACS Appl. Mater. Interfaces

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While the shape effect of nanoparticles on cellular uptake has been frequently studied, no consistent conclusions are available currently. The controversy mainly focuses on the cellular uptake of elongated (i.e., filaments or rod-like micelles) as compared to spherical (i.e., micelles and vesicles) nanoparticles. So far, there is no clear trend that proposes the superiority of spherical or nonspherical nanoparticles with conflicting reports available in the literature. One of the reasons is that these few reports available deal with nanoparticles of different shapes, surface chemistries, stabilities, and aspects ratios. Here, we investigated the effect of the aspect ratio of cylindrical micelles on the cellular uptake by breast cancer cell lines MCF-7 and MDA-MB-231. Cylindrical micelles, also coined rod-like micelles, of various length were prepared using fructose-based block copolymers poly(1-O-methacryloyl-β-d-fructopyranose)-b-poly(methyl methacrylate). The critical water content, temperature, and stirring rate that trigger the morphological transition from spheres to rods of various aspect ratios were identified, allowing the generation of different kinetically trapping morphologies. High shear force as they are found with high stirring rates was observed to inhibit the formation of long rods. Rod-like micelles with length of 500-2000 nm were subsequently investigated toward their ability to translocate in breast cancer cells and penetrate into MCF-7 multicellular spheroid models. It was found that shorter rods were taken up at a higher rate than longer rods.

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Selective Uptake of a Fructose Glycopolymer Prepared by RAFT Polymerization into Human Breast Cancer Cells

Cited by 30 publications

References 29 publications

Enhanced Antimetastatic Activity of the Ruthenium Anticancer Drug RAPTA‐C Delivered in Fructose‐Coated Micelles

Enhanced Antimetastatic Activity of the Ruthenium Anticancer Drug RAPTA‐C Delivered in Fructose‐Coated Micelles

Analysis using size exclusion chromatography of poly( N -isopropyl acrylamide) using methanol as an eluent

Cellular Uptake and Movement in 2D and 3D Multicellular Breast Cancer Models of Fructose-Based Cylindrical Micelles That Is Dependent on the Rod Length

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