Abstract
In this study, pH-responsive prodrug nanoparticles PEG-Schiff-doxorubicin (PEG-Schiff-DOX) were designed and synthesised using chemical conjugation method and can self-assembly into spherical micelles in aqueous solution. These nanoparticles show good storage stability which can be stored over one week under normal condition. The acid-liable Schiff linker is stable under neutral pH and cleave under acidic environment, allowing the prodrug micelles to withhold DOX anticancer drug when being delivered in human circulation and disassemble to release drug once enter tumor cell tissue or taken into intracellular endosomal and lysosomal compartments. In addition to the enhanced permeation and retention (EPR) effect possessed by nanoparticle [1], the nanoparticle prodrug PEG-Schiff-DOX possess an advanced drug release behaviour, resulting in higher intracellular drug concentration in cancer cells and prolonged time of action. The superior anticancer effect of these nanoparticles against Hela cells is also investigated with CCK-8 assays, demonstrating the great potential for clinical application of PEG-Schiff-DOX in cancer treatment.
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