High-Throughput Screening of Polymer Library for mRNA Tumor Vaccine Carriers with Innate Adjuvant Properties

The mRNA-based COVID-19 vaccine has been a tremendous success, instilling hope for the treatment of other malignant diseases. However, the current commercially available mRNA delivery carrier, lipid nanoparticles, still presents certain limitations in treating other illnesses. The development of novel high-performance mRNA delivery carriers remains crucial. Herein, we introduce a novel strategy for constructing mRNA carrier materials. This strategy incorporates multiple interactions, including hydrophobic interaction, π–π conjugation, and hydrogen bonding, within the traditional poly(β-aminoethyl) esters framework to fabricate an extensive library of carriers. The selected polymer P6 balanced the electrostatic interaction and hydrophobic interaction, exhibiting an in vitro transfection efficiency exceeding 98%. Furthermore, a nanovaccine based on P6 and mOVA demonstrated exceptional efficacy in tumor prevention and treatment at an animal level. Additionally, P6 displayed favorable biosafety characteristics. This study identified a carrier material with outstanding performance and provided novel insights into designing high-performance mRNA carriers.