Polymer Nanoparticles Mediated Codelivery of AntimiR-10b and AntimiR-21 for Achieving Triple Negative Breast Cancer Therapy
Open accessAbstract
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 measuredmiR-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).”
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]
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Cites
Silencing of microRNAs in vivo with ‘antagomirs’
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Tumour invasion and metastasis initiated by microRNA-10b in breast cancer
Ma, L., Teruya-Feldstein, J., & Weinberg, R. A. (2007) · Nature · doi:10.1038/nature06174 · Cited by 2,605 · see citing works
MicroRNA-21 Targets a Network of Key Tumor-Suppressive Pathways in Glioblastoma Cells
Papagiannakopoulos, T., Shapiro, A., & Kosik, K. S. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1305 · Cited by 705 · see citing works
The urokinase plasminogen activator system: a target for anti-cancer therapy
Ulisse, S., Baldini, E., Sorrenti, S., & D'Armiento, M. (2009) · Current Cancer Drug Targets · doi:10.2174/156800909787314002 · Cited by 312 · see citing works
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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
- Publisher
- American Chemical Society (ACS)
- Published
- 2015-02-04
- Volume
- 9
- Issue
- 3
- Pages
- 2290-2302
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- PMC
- PMC4374409
- 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
- hybrid
- doi.org
- 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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