Nanoparticle delivery of miR-708 mimetic impairs breast cancer metastasis

Research output: Contribution to journalArticle

Divya Ramchandani, Seung Koo Lee, Shira Yomtoubian, Myung Shin Han, Ching Hsuan Tung, Vivek Mittal

Triple-negative breast cancer (TNBC) patients exhibit the worst clinical outcome due to its aggressive clinical course, higher rate of recurrence, and a conspicuous lack of FDA-approved targeted therapies. Here, we show that multilayered nanoparticles (NPs) carrying the metastasis suppressor microRNA miR-708 (miR708-NP) localize to orthotopic primary TNBC, and efficiently deliver the miR-708 cargo to reduce lung metastasis. Using a SOX2/OCT4 promoter reporter, we identified a population of miR-708 low cancer cells with tumor-initiating properties, enhanced metastatic potential, and marked sensitivity to miR-708 treatment. In vivo, miR708-NP directly targeted the SOX2/OCT4-mCherryþ miR-708 low tumor cells to impair metastasis. Together, our preclinical findings provide a mechanism-based antimetastatic therapeutic approach for TNBC, with a marked potential to generate miR-708 replacement therapy for high-risk TNBC patients in the clinic. To our knowledge, this gold nanoparticle-based delivery of microRNA mimetic is the first oligonucleotide-based targeted therapy for TNBC.

Original languageEnglish (US)
Pages (from-to)579-591
Number of pages13
JournalMolecular Cancer Therapeutics
Volume18
Issue number3
DOIs
StatePublished - Mar 1 2019

PMID: 30679387

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Nanoparticle delivery of miR-708 mimetic impairs breast cancer metastasis. / Ramchandani, Divya; Lee, Seung Koo; Yomtoubian, Shira; Han, Myung Shin; Tung, Ching Hsuan; Mittal, Vivek.

In: Molecular Cancer Therapeutics, Vol. 18, No. 3, 01.03.2019, p. 579-591.

Research output: Contribution to journalArticle

Harvard

Ramchandani, D, Lee, SK, Yomtoubian, S, Han, MS, Tung, CH & Mittal, V 2019, 'Nanoparticle delivery of miR-708 mimetic impairs breast cancer metastasis' Molecular Cancer Therapeutics, vol. 18, no. 3, pp. 579-591. https://doi.org/10.1158/1535-7163.MCT-18-0702

APA

Ramchandani, D., Lee, S. K., Yomtoubian, S., Han, M. S., Tung, C. H., & Mittal, V. (2019). Nanoparticle delivery of miR-708 mimetic impairs breast cancer metastasis. Molecular Cancer Therapeutics, 18(3), 579-591. https://doi.org/10.1158/1535-7163.MCT-18-0702

Vancouver

Ramchandani D, Lee SK, Yomtoubian S, Han MS, Tung CH, Mittal V. Nanoparticle delivery of miR-708 mimetic impairs breast cancer metastasis. Molecular Cancer Therapeutics. 2019 Mar 1;18(3):579-591. https://doi.org/10.1158/1535-7163.MCT-18-0702

Author

Ramchandani, Divya ; Lee, Seung Koo ; Yomtoubian, Shira ; Han, Myung Shin ; Tung, Ching Hsuan ; Mittal, Vivek. / Nanoparticle delivery of miR-708 mimetic impairs breast cancer metastasis. In: Molecular Cancer Therapeutics. 2019 ; Vol. 18, No. 3. pp. 579-591.

BibTeX

@article{6d555bba363a42838a386187bc0afc51,
title = "Nanoparticle delivery of miR-708 mimetic impairs breast cancer metastasis",
abstract = "Triple-negative breast cancer (TNBC) patients exhibit the worst clinical outcome due to its aggressive clinical course, higher rate of recurrence, and a conspicuous lack of FDA-approved targeted therapies. Here, we show that multilayered nanoparticles (NPs) carrying the metastasis suppressor microRNA miR-708 (miR708-NP) localize to orthotopic primary TNBC, and efficiently deliver the miR-708 cargo to reduce lung metastasis. Using a SOX2/OCT4 promoter reporter, we identified a population of miR-708 low cancer cells with tumor-initiating properties, enhanced metastatic potential, and marked sensitivity to miR-708 treatment. In vivo, miR708-NP directly targeted the SOX2/OCT4-mCherry{\th} miR-708 low tumor cells to impair metastasis. Together, our preclinical findings provide a mechanism-based antimetastatic therapeutic approach for TNBC, with a marked potential to generate miR-708 replacement therapy for high-risk TNBC patients in the clinic. To our knowledge, this gold nanoparticle-based delivery of microRNA mimetic is the first oligonucleotide-based targeted therapy for TNBC.",
author = "Divya Ramchandani and Lee, {Seung Koo} and Shira Yomtoubian and Han, {Myung Shin} and Tung, {Ching Hsuan} and Vivek Mittal",
year = "2019",
month = "3",
day = "1",
doi = "10.1158/1535-7163.MCT-18-0702",
language = "English (US)",
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pages = "579--591",
journal = "Molecular Cancer Therapeutics",
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publisher = "American Association for Cancer Research Inc.",
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RIS

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T1 - Nanoparticle delivery of miR-708 mimetic impairs breast cancer metastasis

AU - Ramchandani, Divya

AU - Lee, Seung Koo

AU - Yomtoubian, Shira

AU - Han, Myung Shin

AU - Tung, Ching Hsuan

AU - Mittal, Vivek

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Triple-negative breast cancer (TNBC) patients exhibit the worst clinical outcome due to its aggressive clinical course, higher rate of recurrence, and a conspicuous lack of FDA-approved targeted therapies. Here, we show that multilayered nanoparticles (NPs) carrying the metastasis suppressor microRNA miR-708 (miR708-NP) localize to orthotopic primary TNBC, and efficiently deliver the miR-708 cargo to reduce lung metastasis. Using a SOX2/OCT4 promoter reporter, we identified a population of miR-708 low cancer cells with tumor-initiating properties, enhanced metastatic potential, and marked sensitivity to miR-708 treatment. In vivo, miR708-NP directly targeted the SOX2/OCT4-mCherryþ miR-708 low tumor cells to impair metastasis. Together, our preclinical findings provide a mechanism-based antimetastatic therapeutic approach for TNBC, with a marked potential to generate miR-708 replacement therapy for high-risk TNBC patients in the clinic. To our knowledge, this gold nanoparticle-based delivery of microRNA mimetic is the first oligonucleotide-based targeted therapy for TNBC.

AB - Triple-negative breast cancer (TNBC) patients exhibit the worst clinical outcome due to its aggressive clinical course, higher rate of recurrence, and a conspicuous lack of FDA-approved targeted therapies. Here, we show that multilayered nanoparticles (NPs) carrying the metastasis suppressor microRNA miR-708 (miR708-NP) localize to orthotopic primary TNBC, and efficiently deliver the miR-708 cargo to reduce lung metastasis. Using a SOX2/OCT4 promoter reporter, we identified a population of miR-708 low cancer cells with tumor-initiating properties, enhanced metastatic potential, and marked sensitivity to miR-708 treatment. In vivo, miR708-NP directly targeted the SOX2/OCT4-mCherryþ miR-708 low tumor cells to impair metastasis. Together, our preclinical findings provide a mechanism-based antimetastatic therapeutic approach for TNBC, with a marked potential to generate miR-708 replacement therapy for high-risk TNBC patients in the clinic. To our knowledge, this gold nanoparticle-based delivery of microRNA mimetic is the first oligonucleotide-based targeted therapy for TNBC.

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DO - 10.1158/1535-7163.MCT-18-0702

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EP - 591

JO - Molecular Cancer Therapeutics

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