Cited by 260RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryMicroRNA in disease regulation

Polymer Nanoparticles Mediated Codelivery of AntimiR-10b and AntimiR-21 for Achieving Triple Negative Breast Cancer Therapy

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Devulapally, Rammohan, Sekar, Narayana M., Sekar, Thillai V., Foygel, Kira, Massoud, Tarik F., Willmann, Jürgen K., Paulmurugan, Ramasamy·2015·ACS Nano

Abstract

The current study shows the therapeutic outcome achieved in triple negative breast cancer (TNBC) by simultaneously antagonizing miR-21-induced antiapoptosis and miR-10b-induced metastasis, using antisense-miR-21-PS and antisense-miR-10b-PS delivered by polymer nanoparticles (NPs). We synthesized the antisense-miR-21 and antisense-miR-10b loaded PLGA-b-PEG polymer NPs and evaluated their cellular uptake, serum stability, release profile, and the subsequent synchronous blocking of endogenous miR-21 and miR-10b function in TNBC cells in culture, and tumor xenografts in living animals using molecular imaging. Results show that multitarget antagonization of endogenous miRNAs could be an efficient strategy for targeting metastasis and antiapoptosis in the treatment of metastatic cancer. Targeted delivery of antisense-miR-21 and antisense-miR-10b coloaded urokinase plasminogen activator receptor (uPAR) targeted polymer NPs treated mice showed substantial reduction in tumor growth at very low dose of 0.15 mg/kg, compared to the control NPs treated mice and 40% reduction in tumor growth compared to scramble peptide conjugated NPs treated mice, thus demonstrating a potential new therapeutic option for TNBC.

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  • Inhibition of miR-21 via different strategies elevated apoptotic cell death, sensitivity to chemotherapy/radiotherapy, and diminished tumor progression.

    “Inhibition of miR-21 via different strategies elevated apoptotic cell death, sensitivity to chemotherapy/radiotherapy, and diminished tumor progression (24–28).”

    From Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma (2019) · cites this paper as [24]

    The paper’s Abstract (page unavailable) reports that antisense inhibition of miR-21 induces apoptosis and impairs tumor-cell growth. Its Conclusion (page unavailable) reports reduced tumor growth with combined anti-miR-21/anti-miR-10b nanoparticles. It does not show increased sensitivity to chemotherapy or radiotherapy; the Conclusion proposes combining the approach with chemotherapy as future work. (LLM, conf=0.90)

    Experimental — accuracy not yet measured
  • miR-21 silencing has demonstrated effective results both in vitro and in vivo.

    “In addition, miR-21 silencing has demonstrated effective results both in vitro and in vivo (24–28).”

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Authors
Devulapally, R., Sekar, N. M., Sekar, T. V., Foygel, K., Massoud, T. F., Willmann, J. K., & Paulmurugan, R.
Affiliations
  • Stanford Medicine (US)
  • Stanford University School of Medicine, Stanford University , , 3155 Porter Drive , , ,
Corresponding author
Paulmurugan, Ramasamy
Venue
ACS Nano
Published
2015-02-04
Volume
9
Issue
3
Pages
2290-2302
ISSN
  • 1936-0851 (ISSN-L)
  • 1936-086X
OpenAlex
W2050732886
Cited by
260
References
4
Citations by year
2026: 13 · 2025: 14 · 2024: 11 · 2023: 23 · 2022: 32 · 2021: 30 · 2020: 28 · 2019: 30 · 2018: 27 · 2017: 18 · 2016: 23 · 2015: 10
FWCI
11.30
Type
journal article
Language
en
Open access
Locations
  • ACS Nano (publishedVersion, other-oa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Cancer Institute (R01 CA161091)
  • Canary Center, Stanford University (NA)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Keywords
triple-negative breast cancer, miR-21, miR-10b, polymeric nanoparticles, co-delivery, metastasis, apoptosis, tumor xenografts, molecular imaging, nanoparticle drug delivery
MeSH terms
Animals, Biological Transport, Cell Survival, Cell Transformation, Neoplastic, Drug Carriers, Female, Humans, Neoplasm Invasiveness, Neoplasm Metastasis, Polyethylene Glycols, Polyglactin 910, Genetic Therapy, RNA Stability, MicroRNAs, Cell Line, Tumor, Cell Proliferation, Nanomedicine, Mice, Receptors, Urokinase Plasminogen Activator, Triple Negative Breast Neoplasms

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