Inhibiting Metastatic Breast Cancer Cell Migration via the Synergy of Targeted, pH-triggered siRNA Delivery and Chemokine Axis Blockade

Guo, Peng; You, Jin-Oh; Yang, Jiang; Jia, Di; Moses, Marsha A.; Auguste, Debra T.

doi:10.1021/mp4004699

Cited by 65 publications

(69 citation statements)

References 48 publications

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“…Breast cancer cell ICAM-1 surface protein expression was evaluated by a BD FACSCalibur flow cytometer (BD Biosciences) as described previously (35,36). Quantification of the ICAM-1 density on the cell surface was determined with reference to Quantum Simply Cellular microbeads, using the protocol as provided by the manufacturer.…”

Section: Methodsmentioning

confidence: 99%

ICAM-1 as a molecular target for triple negative breast cancer

Guo

Huang

Wang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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153

137

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Triple negative breast cancers (TNBCs) have a high mortality rate owing to aggressive proliferation and metastasis and a lack of effective therapeutic options. Herein, we describe the overexpression of intercellular adhesion molecule-1 (ICAM-1) in human TNBC cell lines and tissues, and demonstrate that ICAM-1 is a potential molecular target and biomarker for TNBC therapy and diagnosis. We synthesized ICAM-1 antibody-conjugated iron oxide nanoparticles (ICAM-IONPs) as a magnetic resonance imaging (MRI) probe to evaluate tumor targeting. Quantitative analysis of ICAM-1 surface expression predicted the targeting capability of ICAMIONPs to TNBC cells. MRI of the TNBC xenograft tumor after systemic administration of ICAM-IONPs, coupled with iron quantification and histology, demonstrated a significant and sustained MRI contrast enhancement and probe accumulation in tumors with ICAM-1 overexpression relative to control. Identification of ICAM-1 as a TNBC target and biomarker may lead to the development of a new strategy and platform for addressing a critical gap in TNBC patient care.

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Section: Methodsmentioning

confidence: 99%

ICAM-1 as a molecular target for triple negative breast cancer

Guo

Huang

Wang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

153

137

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“…Chemokine networks are thus an important emerging target for development of novel drug delivery strategies (25). By devising systems capable of simultaneous CXCR4 inhibition and delivery of antitumor agents, it should be possible to improve the overall anticancer activity (26).…”

Section: Introductionmentioning

confidence: 99%

Polymeric Plerixafor: Effect of PEGylation on CXCR4 Antagonism, Cancer Cell Invasion, and DNA Transfection

Wang

Oupický

2014

Pharm Res

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Purpose To determine the effect of PEG modification on pharmacologic and gene delivery properties of polymeric CXCR4 antagonist based on Plerixafor. Methods Polymeric Plerixafor (PAMD) was synthesized from Plerixafor (AMD3100) and grafted with different amounts of PEG (2 kDa). CXCR4 antagonism of the synthesized polymers was determined using receptor redistribution assay. Inhibition of cancer cell invasion by the polyplexes of the synthesized polymers was assessed using Boyden-chamber method. Transfection activity of DNA polyplexes formed with the synthesized polymers was evaluated in U2OS osteosarcoma and B16F10 melanoma cells. Results Our results demonstrate that modification of PAMD with PEG decreased toxicity of the polymers, while preserving their CXCR4 antagonism. Polyplexes prepared with PEG-PAMD inhibited invasion of cancer cells to an extent similar to the commercial CXCR4 antagonist Plerixafor. Negative effect of PEG on transfection activity of PEG-PAMD polyplexes could be overcome by using polyplexes formulated with a mixture of PAMD and PEG-PAMD. Conclusion Modification of PAMD with PEG is a viable strategy to preserve the desirable CXCR4 antagonism and ability to inhibit cancer cell invasion of PAMD, while improving safety and colloidal stability of the PAMD polyplexes.

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“…Human MM cell migration was measured as described previously [25]. Briefly, A375SM and C32 cells were pre-treated with the following samples: IgG, ICAM-1 antibody, IgG-LP, ICAM-LP for 24 h, and then seeded onto COSTAR migration inserts with permeable support polycarbonate membrane (8 μm pore size) in a 24-well plate at a cell density of 10 5 cells per well in DMEM without FBS.…”

Section: Methodsmentioning

confidence: 99%

“…The density of ICAM-1antibodies conjugated on liposomes was quantified via microbead assay as described previously [25–27]. Liposomes cannot be detected by flow cytometry because of their size, therefore, 2 μm borosilicate beads were encapsulated within DOPC: DSPE-PEG-COOH (95:5, mol:mol) liposomes by sonicating small unilamellar liposomes with microbeads in PBS for 6 h. Microbeads were rinsed three times in PBS via suspension-spin cycles to separate free liposomes.…”

Section: Methodsmentioning

confidence: 99%

A quantitative method for screening and identifying molecular targets for nanomedicine

Guo

Yang

Bielenberg

et al. 2017

Journal of Controlled Release

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Identifying a molecular target is essential for tumor-targeted nanomedicine. Current cancer nanomedicines commonly suffer from poor tumor specificity, “off-target” toxicity, and limited clinical efficacy. Here, we report a method to screen and identify new molecular targets for tumor-targeted nanomedicine based on a quantitative analysis. In our proof-of-principle study, we used comparative flow cytometric screening to identify ICAM-1 as a potential target for metastatic melanoma (MM). We further evaluated ICAM-1 as a MM targeting moiety by characterizing its (1) tumor specificity, (2) expression level, (3) cellular internalization, (4) therapeutic function, and (5) potential clinical impact. Quantitation of ICAM-1 protein expression on cells and validation by immunohistochemistry on human tissue specimens justified the synthesis of antibody-functionalized drug delivery vehicles, which were benchmarked against appropriate controls. We engineered ICAM-1 antibody conjugated, doxorubicin encapsulating immunoliposomes (ICAM-Dox-LPs) to selectively recognize and deliver doxorubicin to MM cells and simultaneously neutralize ICAM-1 signaling via an antibody blockade, demonstrating significant and simultaneous inhibitory effects on MM cell proliferation and migration. This paper describes a novel, quantitative metric system that identifies and evaluates new cancer targets for tumor-targeting nanomedicine.

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Inhibiting Metastatic Breast Cancer Cell Migration via the Synergy of Targeted, pH-triggered siRNA Delivery and Chemokine Axis Blockade

Cited by 65 publications

References 48 publications

ICAM-1 as a molecular target for triple negative breast cancer

ICAM-1 as a molecular target for triple negative breast cancer

Polymeric Plerixafor: Effect of PEGylation on CXCR4 Antagonism, Cancer Cell Invasion, and DNA Transfection

A quantitative method for screening and identifying molecular targets for nanomedicine

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