The degree of modification was determined by 1 H-NMR from the ratio between the relative peak areas of methylene backbone of PEI (δ 2.45-3.6 ppm) and succinyl protons (δ 2.25-2.45 ppm) or methyl protons of acetate (δ 1.85-2.1 ppm). 2D-NMR (HSQC and HMBC) spectra were acquired to enable the assignment of the modified PEI peaks. (Supplementary information, Figure Ethidium Bromide Displacement Assay. The affinity for PEI and modified PEIs for binding DNA was followed by the ethidium bromide (EtBr) displacement assay. Stock solutions of calfthymus DNA and EtBr were prepared by dissolving in 10 mM Tris-HCl buffer (pH 7.5) overnight to a final concentration of 0.24 µg/µL and 0.024 µg/µL, respectively. 12 µg of ctDNA in Tris buffer (pH 7.5) was incubated with 1.2 µg EtBr at room temperature for 10 min. This corresponds to a labeling ratio of approximately 1 EtBr per 10 DNA base pairs. After incubation of the DNA with EtBr, the desired volume and concentration of polymer stock solutions were added to achieve the desired nitrogen-to-phosphate (N/P) ratio. The resulting polyplexes were incubated for another 30 min at room temperature. After incubation, the final volume was adjusted to 500 μL using 10 mM Tris buffer before measurement by fluorescence spectroscopy. Measurements were performed with samples in a quartz cuvette. The fluorescence intensity of the polyplex solutions was recorded on a Thermo Lumina Fluorescence Spectrometer at λex = 520 nm and λem = 610 nm. Samples of ctDNA/EtBr without PEI and free EtBr were also measured as positive and negative controls. The percentage of EtBr displaced upon polyplex formation was calculated by determining the relative fluorescence (rf%) = [(F-Fo)/(FMax-Fo)] *100, where F, Fo, and FMax are the emission intensity of the sample, the EtBr alone, and ctDNA/EtBr control, respectively.