We use the soft lithography process Particle Replication in Non-wetting Templates (PRINT) to construct uniform polymer nanoparticles containing sensitive biological cargo such as small interfering RNA (siRNA) or antisense oligonucleotides. The PRINT process effectively yielded 200nm x 200nm cylindrical particles with a narrow size and shape distribution, and the nucleotide-based therapeutics were directly incorporated during the particle fabrication process. Particles for the studies reported herein were constructed of poly(N-vinyl pyrrolidone) (PVP) copolymerized with disulfide crosslinkers known to cleave under endosomal conditions. These particles delivered anti-luciferase siRNA to a luciferase-transfected HeLa reporter cell line. Efficient uptake of the cargo-loaded particles by the cells was confirmed using fluorescein-labeled particles and FACS. Cargo delivery and cell viability were quantified using luciferase knockdown and toxicity assays with appropriate controls. Ongoing in vitro experiments aim to prepare particles that more efficiently degrade and release cargo upon endosomal uptake, and thus far dose-dependent luciferase knockdown as high as 40% has been observed.