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Additive Polyplexes to Undertake siRNA Therapy against CDC20 and Survivin in Breast Cancer Cells

Manoj B Parmar, Remant Bahadur K C, Raimar Löbenberg

    Biomacromolecules
    |September 18, 2018
    PubMed

    Insights

    New siRNA delivery agents using additive polyplexes show promise for treating breast cancer by silencing overexpressed genes. Careful formulation is needed to minimize side effects on normal cells.

    Area of Science:

    • Biotechnology
    • Nanomedicine
    • Cancer Therapy

    Background:

    • Small interfering RNA (siRNA) offers targeted therapy for malignancies by silencing overexpressed genes.
    • Developing effective siRNA delivery systems is crucial for cancer treatment.
    • Uncontrolled cell growth in cancers necessitates novel therapeutic strategies.

    Purpose of the Study:

    • To formulate and characterize additive polyplexes for enhanced siRNA delivery.
    • To evaluate the efficacy of these polyplexes in breast cancer cells.
    • To assess potential side effects and optimize formulation for normal cells.

    Main Methods:

    • Formulation of siRNA polyplexes using linoleic acid-substituted polyethylenimine and additive polymers (hyaluronic acid, poly(acrylic acid), dextran sulfate, methyl cellulose).
    • Characterization of physicochemical properties (e.g., ζ-potential) and cellular delivery efficiency.
    • In vitro efficacy testing of CDC20 and survivin siRNAs in various breast cancer cell lines (MDA-MB-231, SUM149PT, MDA-MB-436, MCF7).

    Main Results:

    • Incorporating polyanionic polymers decreased polyplex ζ-potential but enhanced cellular siRNA delivery.
    • Additive polyplexes demonstrated promising efficacy in silencing target genes in multiple breast cancer cell lines.
    • Side effects were observed in nonmalignant cells, highlighting the need for formulation optimization.

    Conclusions:

    • Additive polyplexes represent a potent strategy for siRNA delivery in breast cancer therapy.
    • The efficacy of this delivery system is independent of specific breast cancer phenotypes.
    • Further development is warranted to minimize off-target effects and advance clinical application.

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