Machine Learning Reveals Amine Type in Polymer Micelles Determines mRNA Binding, <i>In Vitro, and In Vivo</i> Performance for Lung-Selective Delivery.

ABSTRACT: Cationic micelles, composed of amphiphilic block copolymers with polycationic coronas, offer a customizable platform for mRNA delivery. Here, we present a library of 30 cationic micelle nanoparticles (MNPs) formulated from diblock copolymers with reactive poly(pentafluorophenol acrylate) backbones modified with diverse amines. This library systematically varies in nitrogen-based cationic functionalities, exhibiting a spectrum of properties that encompass varied degrees of alkyl substitution (A1-A5), piperazine (A6), oligoamine (A7), guanidinium (A8), and hydroxylation (A9-A10) that vary in side-chain volume, substitution pattern, hydrophilicity, and pK _a to assess parameter impact on mRNA delivery. In vitro delivery assays using GFP+ mRNA across multiple cell lines

SUBMITTER: Panda S 

PROVIDER: S-EPMC12041957 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature