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Supplementary Figures S1-S10 from Nanoparticle Delivery of miR-708 Mimetic Impairs Breast Cancer Metastasis

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posted on 2023-04-03, 15:28 authored by Divya Ramchandani, Seung Koo Lee, Shira Yomtoubian, Myung Shin Han, Ching-Hsuan Tung, Vivek Mittal

Supplementary Figure S1. Cell cytotoxicity of NPs in MDA-MB-231 cells; Supplementary Figure S2. Localization of AuNP-cy5.5 in primary tumors; Supplementary Figure S3. Wound healing/Cell Migration Assay; Supplementary Figure S4. In vitro invasion after miR708-NP treatment; Supplementary Figure S5. Effect of miR-708 on Cell Proliferation; Supplementary Figure S6. Effect of miR-708 on Apoptosis; Supplementary Figure S7. Mammosphere formation in SORE6- versus SORE6+ cells; Supplementary Figure S8. Effect of AuNPs on myeloid population; Supplementary Figure S9. Effect of AuNPs on T-cells; Supplementary Figure S10. Effect of AuNPs on effector cytokines.

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U.S. Department of Defense

Clinical and Translation Science

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ARTICLE 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-708low 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+ miR-708low 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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    Molecular Cancer Therapeutics

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    Keywords

    Breast CancerDrug TargetsNanoparticle AgentsProgression, Invasion & Metastasis

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    CC BY

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