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 (PELA x ) nanoparticles (NPs)-pH7.4 with different poly(2-azepane ethyl methacrylate) (PAEMA) lengths and PELA4 nanoparticles (NPs)-pH x with different pH conditions of preparing NPs based on mPEG 113 - b -PCL x - b -PAEMA y are prepared to investigate influences of PAEMA lengths and pH condition of preparing NPs on properties of NPs. PELA x NPs-pH7.4 and PELA4 NPs-pH x both undergo differently sharp property changes of size, charge, pH-responsive drug release, cellular uptake, and cytotoxicity, because of the protonation of PAEMA block (p K a ≈ 6.5–6.7). Among PELA x NPs-pH7.4 and PELA4 NPs-pH x , it can be found that the NPs prepared at p K 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.