pH-Responsive Nanoparticles for Controllable Curcumin Delivery: The Design of Polycation Core with Different Structures

To achieve low leakage at pH 7.4, pH-controlled drug release remains a major challenge of cancer nanomedicine. Here, pH-responsive mPEG(113)-b-polycaprolactone (PCL)(x)-b-PAEMA(y) (PELAx) nanoparticles (NPs)-pH7.4 with different poly(2-azepane ethyl methacrylate) (PAEMA) lengths and PELA4 nanoparticles (NPs)-pHx with different pH conditions of preparing NPs based on mPEG(113)-b-PCLx-b-PAEMA(y) are prepared to investigate influences of PAEMA lengths and pH condition of preparing NPs on properties of NPs. PELAx NPs-pH7.4 and PELA4 NPs-pHx both undergo differently sharp property changes of size, charge, pH-responsive drug release, cellular uptake, and cytotoxicity, because of the protonation of PAEMA block (pKa approximate to 6.5-6.7). Among PELAx NPs-pH7.4 and PELA4 NPs-pHx, it can be found that the NPs prepared at pK(a) value of PAEMA exhibited exciting pH-responsive drug release, improving cellular uptake ability and obvious high cytotoxicity toward HepG-2 cells. This system not only holds great potential for drug delivery but also provides a new strategy to prepare pH-responsive NPs.