Poly(I:C) Lipoamino Bundle LNPs Induce Tumor Cytotoxicity and Immune Activation with Enhanced Efficacy by Survivin

Mina Yazdi1,2, Zahra Hasheminejad1, Khouloud Hachani3

  • 1Pharmaceutical Biotechnology, Department of Pharmacy, Ludwig-Maximilians-Universität (LMU), 81377 Munich, Germany.

Insights

Synthetic polyinosinic:polycytidylic acid (poly(I:C)) shows promise as a cancer therapy. New lipoamino fatty acid xenopeptide (LAF-XP) carriers effectively deliver poly(I:C) into cells, enhancing anti-tumor activity and immune responses.

Area of Science:

  • Nanotechnology
  • Immunology
  • Oncology

Background:

  • Synthetic polyinosinic:polycytidylic acid (poly(I:C)) has dual anticancer functions: direct tumor cell killing and immunostimulation.
  • Effective intracellular delivery of poly(I:C) is crucial for activating its receptors and maximizing therapeutic potential.

Purpose of the Study:

  • To develop efficient pH-responsive formulations for intracellular delivery of poly(I:C).
  • To evaluate the anti-tumoral activity and immunomodulatory effects of poly(I:C) delivered via novel lipoamino fatty acid xenopeptide (LAF-XP) carriers.

Main Methods:

  • Formulation of poly(I:C)-lipid nanoparticles (LNPs) using LAF-XP carriers (bundle LAF4-Stp1).
  • Assessment of anti-tumoral activity in various cancer cell models.
  • Evaluation of immune responses, including CXCL10 production and peripheral blood mononuclear cell (PBMC) activation (phenotypic markers and cytokine production).
  • Combination therapy with siRNA-mediated survivin knockdown.

Main Results:

  • LAF-XP LNP-formulated poly(I:C) demonstrated enhanced anti-tumoral activity at lower doses compared to controls.
  • Delivery of poly(I:C) via LAF-XP LNPs stimulated immune responses, evidenced by increased CXCL10, CD69, LAMP-1/CD107a, IFN-γ, and granzyme B.
  • Conditioned PBMC supernatant reduced cancer cell viability, indicating immune-mediated tumor cell death.
  • Combined poly(I:C) and survivin siRNA delivery via LAF-XP LNP increased cancer cell apoptosis.

Conclusions:

  • Efficient LAF-XP LNPs serve as a versatile platform for delivering poly(I:C).
  • This platform supports multi-layered therapeutic strategies, including combined immunotherapy and gene silencing, for enhanced cancer treatment.

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