Figure 1.

A combinatorial library of functional polyester NPs was screened in IGROV1 cells to optimize mRNA delivery materials. A library of 1200 functional polyesters was chemically synthesized for the screening of mRNA delivery. Polyesters were modified with amino thiols (R₁SH) and alkyl thiols (R₂SH) to generate a combinatorial polymer library. Amino thiols are named A followed by a number; alkyl thiols are named SC or SO followed by the number of carbons. Functional polyesters with Mw 4200 g/mol (PE4K), 8300 g/mol (PE8K), and 17,000 g/mol (PE17K) were modified with five amino thiols (A3, A5, A6, A17, and A21) and all 20 alkyl thiols at SC:A molar feed ratios of 1:4, 1:2, 1:1, and 2:1. Functionalized polymers are named by the polyester Mw, amino modification, and the mole fraction of alkyl modification. All functional polyesters were examined for in vitro mRNA delivery efficacy. Selected functional polyesters (0.2C4 to 0.2C11; 0.3C5 to 0.3C9) were examined for in vivo mRNA delivery efficacy.