pH and reduction-activated polymeric prodrug nanoparticles based on a 6-thioguanine-dialdehyde sodium alginate conjugate for enhanced intracellular drug release in leukemia

摘要: For enhanced intracellular drug release in leukemia, the structure of 6-thioguanine (6-TG) based pH/reduction responsive polymeric prodrug nanoparticles was constructed by conjugating 6-TG to dialdehyde sodium alginate (DSA) via acid-labile Schiff base linkage followed ultrasound-assisted oxidation thiol groups disulfide cross-links. The are stable at pH 7.4 containing 0 and 10 μM glutathione (GSH) with almost no release, but a cumulative rate up 98.6% 228 h observed 5.0 20 mM GSH first 48 hours over three times as much that case GSH, indicating dual-stimulation can significantly elevate tumour cell-selective release. In comparison free 6-TG, this system exhibited slightly higher inhibition ratio on HL-60 cancer cells, while an obviously reduced cytotoxicity for healthy liver cell line L-O2. Furthermore, vitro studies further confirmed efficient cellular uptake cells.