Dual pH-responsive charge-reversal and photo-crosslinkable polymer nanoparticles for controlled drug release.

In this article, we introduce a pH-responsive charge-reversible and photo-crosslinkable polymer nanoparticle. It is prepared via typical self-assembly from a block copolymer poly((7-(4-vinyl-benzyloxyl)-4-methylcoumarin)-co-acrylicacid)-b-poly((2-dimethylamino) ethyl methacrylate)-co-styrene) (P(VBMC-co-AA)-b-P(DMAEMA-co-St)), whose two blocks have different ionizable moieties. In an aqueous solution of pH ≤ 4, the cationic polymer nanoparticles are formed due to the fully protonated PDMAEMA. At a pH ranging from 5.0 to 7.8, partially ionized PAA and protonated PDMAEMA lead to the formation of polymer nanoparticles with a mixed shell. In a pH range of 8-10, a large amount of precipitation is produced within the isoelectric point (IEP) region because of the weak hydrophilic two blocks. In an aqueous solution of pH ≥ 10, polymer nanoparticles are reformed with PAA shell and P(DMAEMA-co-St) core. The coumarin groups of polymer can undergo photo-crosslinking and photo-cleavage reactions under UV light irradiation at λ = 365 nm and λ = 254 nm, respectively. The reversible nature of the photo-reaction can regulate the reversal of polymer nanoparticles. Furthermore, the aggregation-induced fluorescence emission (AIFE) property of polymer nanoparticles at different pH is tested by fluorescence emission spectra. The results indicate that the aggregation state of coumarin blocks in solution also changes with the pH value. The DOX release experiment in vitro shows that the release behavior of DOX-loaded nanoparticles can be adjusted by pH and light to achieve significant control. The inhibitory effect on the growth of tumor cells is displayed by cellular uptake and cytotoxicity test in vitro. The self-assembly system of polymer nanoparticles can be cooperatively controlled by multiple stimulations and displays potential applications in controlled drug delivery.