Integration of PEG and PEI with graphene quantum dots to fabricate pH-responsive nanostars for colon cancer suppression in vitro and in vivo

The proposed drug release mechanism after entering the tumor cell. [Display omitted] •PEG and PEI conjugated GQDs, to form pH-responsive nanostar drug carrier.•GQDs-polymer-DOX conjugates (GECD) as drug carrier for colon cancer suppression investigation.•GECD nanostar from neutral to mild positive, possessed higher affinity to negatively charged cell membrane.•The in vivo and in vitro results indicate that GECD nanostar with high cancer suppression capacity. There has been great improvement in nanomaterial fields, and the biomedical potential of nanomaterials as drug delivery system is under intensive studies. Among them, graphene quantum dots (GQDs) are considered to be the next generation of carbon-based nanomaterial for biomedical applications. In this study, we utilized green fluorescent protein (GFP) nucleic acid, DNA-targeting chemoreagent doxorubicin (DOX), and branched polyethyleneimine (PEI) conjugated GQDs, to form pH-responsive nanostar drug carrier for colon cancer suppression investigation. GFP expression plasmid was applied to examine the delivery capacity of our drug carrier. DOX was encapsulated by intrinsic π-π interaction to form GQDs-polymer-DOX conjugates (GECD) as drug carrier. We proposed that once GECD enters the tumor lesion, the acidic tumor microenvironment protonated the tertiary amine of GECD from neutral to mild positive, possessed higher affinity to negatively charged cell membrane, triggered the drug release, and then cancer cells would be inhibited. The anti-cancer ability of our drug carrier system, GECD, was demonstrated in cancer cells by cell proliferation assay. Moreover, GECD exhibited its powerful anti-tumor capacity in the mice xenograft model. The in vivo and in vitro results indicate that our GECD with high cancer suppression capacity could be adopted for future cancer therapy.