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

ABSTRACT: Oral squamous cell carcinoma (OSCC) treatment is challenged by disrupted microRNA (miRNA) regulation, making efficient miRNA delivery essential. Here, we synthesized and screened Pluronic-polyethylenimine (Pluronic-PEI) nanocarriers for miRNA delivery in OSCC. Among several Pluronic variants, only L121 formed stable, fully cross-linked micellar nanogels with low-molecular-weight PEI (1.8 kDa), designated PP03. Its monomodal size, rough 3D morphology, and zeta potential > +30 mV provide colloidal stability and allow electrostatic miRNA complexation. The presence of a pH-sensitive ester linkage may enable endosomal escape through PEI's proton sponge effect, combined with Pluronic-mediated osmotic modulation, which promotes the release of the therapeutic cargo at the site of action. These fin

SUBMITTER: Domingues C 

PROVIDER: S-EPMC12818751 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature