Graphene aerogel nanoparticles for in-situ loading/pH sensitive releasing anticancer drugs

Free polymer graphene aerogel nanoparticles (GA NPs) were synthesized by using reduction/aggregation of graphene oxide (GO) sheets in the presence of vitamin C (as a biocompatible reductant agent) at a low temperature (40 °C), followed by an effective sonication. Synthesis of GA NPs in doxorubicin hydrochloride (DOX)-containing solution results in the simultaneous synthesis and drug loading with higher performance (than that of the separately synthesized and loaded samples). To investigate the mechanism of loading and the capability of GA NPs in the loading of other drug structures, two groups of ionized (DOX, Amikacin sulfate and, d-glucosamine hydrochloride) and non-ionized (Paclitaxel (PTX)) drugs were examined. Furthermore, the relationship between the bipolar level of DOX solution (contributing to H-bonding of DOX and GO) and the amount of DOX loading was investigated. The DOX showed higher loading (>3 times) than PTX, as anticancer drugs. Since both DOX and PTX possess aromatic structures, the higher loading of DOX was assigned to its positive partial charge and ionized nature. Accordingly, other drugs (having positive partial charge and ionized nature, but no aromatic structure) such as Amikacin sulfate and d-glucosamine hydrochloride presented higher loading than PTX. These results indicated that although the π-π interactions induced by aromatic structures are important in drug loading, the electrostatic interaction of ionized drugs with GO (especially through H-bonding) is the dominant mechanism. DOX-loaded GANPs showed high pH-sensitive release (equivalent to the carrier weight) after 5 days, which can indicate benefits in tumor cell acidic microenvironments in-vivo.