Liposomes-Encapsulating Double-Stranded Nucleic Acid (Poly I:C) for Head and Neck Cancer Treatment
Vidit Singh1, Anna Chernatynskaya1, Lin Qi1
1Linda and Bipin Doshi Department of Chemical and Biochemical Engineering, Missouri University of Science and Technology, Rolla 65409, Missouri, United States.
Abstract:
Polyriboinosinic acid-polyribocytidylic acid (Poly I:C) serves as a synthetic mimic of viral double-stranded dsRNA, capable of inducing apoptosis in numerous cancer cells. Despite its potential, therapeutic benefits, the application of Poly I:C has been hindered by concerns regarding toxicity, stability, enzymatic degradation, and undue immune stimulation, leading to autoimmune disorders. To address these challenges, encapsulation of antitumor drugs within delivery systems such as cationic liposomes is often employed to enhance their efficacy while minimizing dosages. In this study, we investigated the potential of cationic liposomes to deliver Poly I:C into the Head and Neck 12 (HN12) cell line to induce apoptosis in the carcinoma cells and tumor model. Cationic liposomes made by the hydrodynamic focusing method surpass traditional methods by offering a continuous flow-based approach for encapsulating genes, which is ideal for efficient tumor delivery. DOTAP liposomes efficiently bind Poly I:C, confirmed by transmission electron microscopy images displaying their spherical morphology. Liposomes are easily endocytosed in HN12 cells, suggesting their potential for therapeutic gene and drug delivery in head and neck squamous carcinoma cells. Activation of apoptotic pathways involving MDA5, RIG-I, and TLR3 is evidenced by upregulated caspase-3, caspase-8, and IRF3 genes upon endocytosis of Poly(I:C)-encapsulated liposomes. Therapeutic evaluations revealed significant inhibition of tumor growth with Poly I:C liposomes, indicating the possibility of MDA5, RIG-I, and TLR3-induced apoptosis pathways via Poly I:C liposomes in HN12 xenografts in J:NU mouse models. Comparative histological analysis underscores enhanced cell death with Poly I:C liposomes, warranting further investigation into the precise mechanisms of apoptosis and inflammatory cytokine response in murine models for future research.
Insights
Cationic liposomes effectively deliver Polyriboinosinic acid-polyribocytidylic acid (Poly I:C) to head and neck cancer cells, inducing apoptosis and inhibiting tumor growth. This approach enhances Poly I:C
Area of Science:
- Oncology
- Nanotechnology
- Immunology
Background:
- Polyriboinosinic acid-polyribocytidylic acid (Poly I:C) mimics viral dsRNA and induces cancer cell apoptosis.
- Challenges with Poly I:C therapy include toxicity, instability, and immune overstimulation.
- Cationic liposomes are explored as delivery systems to improve drug efficacy and reduce dosage.
Purpose of the Study:
- To investigate cationic liposomes for delivering Poly I:C to Head and Neck 12 (HN12) cells.
- To assess Poly I:C liposome-induced apoptosis in head and neck squamous cell carcinoma.
- To evaluate the therapeutic efficacy of Poly I:C liposomes in a murine tumor model.
Main Methods:
- Utilized hydrodynamic focusing for continuous flow liposome production.
- Confirmed Poly I:C encapsulation and liposome morphology via transmission electron microscopy.
- Assessed liposome endocytosis in HN12 cells and gene expression of apoptotic markers (caspase-3, caspase-8, IRF3).
- Evaluated tumor growth inhibition in HN12 xenografts in J:NU mice.
Main Results:
- DOTAP liposomes demonstrated efficient Poly I:C binding and spherical morphology.
- Liposomes were readily endocytosed by HN12 cells.
- Upregulation of MDA5, RIG-I, TLR3, caspase-3, caspase-8, and IRF3 confirmed apoptotic pathway activation.
- Significant tumor growth inhibition was observed in the Poly I:C liposome treatment group.
- Histological analysis showed enhanced cell death in Poly I:C liposome-treated tumors.
Conclusions:
- Cationic liposomes are a promising delivery system for Poly I:C in head and neck cancer therapy.
- Poly I:C liposomes effectively induce apoptosis in HN12 cells and inhibit tumor growth in vivo.
- Further research is warranted to elucidate precise apoptosis mechanisms and inflammatory responses.
