Optimizing Pluronic-PEI Nanocarriers for RNAi Delivery in Oral Cancer: From Polymer Synthesis to Functional Screening

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Research

Background:

• Oral squamous cell carcinoma (OSCC) treatment faces challenges due to dysregulated microRNA (miRNA) activity.
• Effective delivery of therapeutic miRNAs is crucial for improving OSCC treatment outcomes.

Purpose of the Study:

• To synthesize and evaluate Pluronic-polyethylenimine (Pluronic-PEI) nanocarriers for efficient miRNA delivery in OSCC.
• To investigate the potential of these nanocarriers in reducing OSCC cell proliferation and tumor growth.

Main Methods:

• Screening of various Pluronic variants to identify optimal nanocarrier properties.
• Characterization of the selected nanocarrier (PP03) for size, morphology, zeta potential, and stability.
• Assessment of miRNA complexation, endosomal escape mechanisms, and therapeutic efficacy in OSCC cell cultures (2D and 3D).

Main Results:

• A specific Pluronic-PEI formulation (PP03) formed stable, monomodal nanogels with favorable characteristics for miRNA delivery.
• PP03 demonstrated efficient complexation and electrostatic delivery of miRNA100.
• Delivered miRNA100 significantly reduced OSCC cell metabolic activity and spheroid size, especially in metastatic models.
• PP03 exhibited mucoadhesion and hemocompatibility, suggesting versatile administration routes.

Conclusions:

• Pluronic-PEI nanocarriers, specifically PP03, show significant promise for enhancing oral cancer therapy through effective miRNA delivery.
• The developed nanocarrier system offers a potential strategy to overcome challenges in miRNA delivery for OSCC treatment.
• This work highlights the importance of polymer chemistry in designing functional nanocarriers for targeted cancer therapy.