Surface spermidine functionalized PEGylated poly(lactide-co-glycolide) nanoparticles for tumor-targeted drug delivery

Abstract

Development of targeted drug delivery systems for tumor therapy provides an effective approach to minimize the side effects originating from arbitrary in vivo drug distribution after systemic administration. In this study, we reported DOX-loaded PEG–PLGA nanoparticles with the surface modified with spermidine (SPD) (SPD–DOX-NPs) for targeted delivery of DOX into tumor cells, which benefits from the polyamine transport system (PTS) on the tumor cell surface. The as-prepared NPs showed a typical spherical morphology with about 150 nm diameter and near electric neutrality of surface charge. The in vitro drug release displayed a sustained release profile. Characterization by fluorescence microscopy and flow cytometry revealed that the cellular uptake of SPD–DOX-NPs in A549 cells depends on SPD content on the surface of the particles. The uptake efficiency can be further increased by adding eflornithine (DMFO) and competitively inhibited by free SPD pre-treatment. These results collectively suggest that PTS is essential for particle internalization. Furthermore, the SPD–DOX-NPs exhibited significantly enhanced cytotoxicity towards A549 cells than the free DOX solution and SPD-free DOX-NPs. Taken together, our results demonstrate that SPD-functionalized nanoparticles are a potential candidate for targeted delivery of drugs into tumor cells.