Dual pH- and GSH-Responsive Degradable PEGylated Graphene Quantum Dot-Based Nanoparticles for Enhanced HER2-Positive Breast Cancer Therapy.

Dual stimuli-responsive degradable carbon-based nanoparticles (DS-CNPs) conjugated with Herceptin (HER) and polyethylene glycol (PEG) have been designed for the treatment of HER2-positive breast cancer. Each component has been linked through disulfide linkages that are sensitive to glutathione in a cancer microenvironment. beta-cyclodextrin (beta-CD) on the surface of DS-CNPs formed an inclusion complex (DL-CNPs) with doxorubicin (DOX) at a high loading capacity of 5.3 +/- 0.4%. In response to a high level of glutathione (GSH) and low pH in a tumor environment, DL-CNPs were rapidly degraded and released DOX in a controlled manner via disruption of host-guest inclusion. These novel DL-CNPs exhibited high cellular uptake with low toxicity, which induced the efficient inhibition of antitumor activity both in vitro and in vivo. Cell viability, confocal laser scanning microscopy, and animal studies indicate that DL-CNPs are a great platform with a synergistically enhanced antitumor effect from the dual delivery of HER and DOX in DL-CNPs.