Ultrasonically assisted preparation of poly(acrylic acid)/calcium phosphate hybrid nanogels as pH-responsive drug carriers

- Stable PAA/CaP hybrid nanogels are ultrasonically synthesized without extra cross-linker.
- The formation relies on the cross-linking between Ca2 + ions of CaP nanoparticles and -COOH groups of PAA molecules.
- They display an enhanced loading capacity for DOX compared to pure CaP nanoparticles.
- They can deliver drug into cancer cells and show a pH-controlled drug release in intracellular acidic environment.

Biocompatible, biodegradable and stimuli-responsive nanomaterials can be used as drug carriers and to achieve controlled drug delivery, which is crucial for treating tumors and lowering drug side effects. Calcium phosphate (CaP) nanoparticles and poly(acrylic acid) (PAA) hydrogels can be used as biocompatible and pH-responsive drug carriers. In this study, based on the ultrasound effect, PAA/CaP hybrid nanogels (approximately 100 nm, PDI < 0.2) are obtained via the cross-linking of CaP nanoparticles and PAA molecules between the Ca2 + ions and -COOH groups. The PAA/CaP hybrid nanogels show good stability in biological media as well as no hemolysis and no cytotoxicity to L02 cells. Moreover, the PAA/CaP hybrid nanogels display an enhanced loading capacity (approximately 32%) for doxorubicin hydrochloride (DOX) compared to pure CaP nanoparticles (approximately 7.5%) and a pH-controlled drug release due to their dissolution in acidic environment. DOX can be delivered into cancer cells by the PAA/CaP hybrid nanogels, which show an inhibitory effect comparable to that of free DOX, although the inhibitory effect is delayed due to the slow release of DOX from the carriers. In vivo, the PAA/CaP hybrid nanogels cannot avoid the capture by the reticuloendothelial system; however, they show passive tumor targeting ability. In brief, the biocompatible, biodegradable and pH-responsive PAA/CaP hybrid nanogels have the potential to act as drug carriers for controlled drug release.