Redox-Sensitive Prodrug Molecules Meet Graphene Oxide: An Efficient Graphene Oxide-Based Nanovehicle toward Cancer Therapy

The stability and slow and incomplete drug release are the key problems for graphene oxide nanocarrier systems. To solve the above problems, we constructed a new drug delivery system from the graphene oxide (GO) decorated with the redox-sensitive prodrug molecules for cancer therapy. PEG-PCL-SS-DOX (prodrug) was synthesized by linking the anticancer drug doxorubicin (DOX) to the biodegradable and biocompatible amphiphilic copolymers PEG-PCL via redox-sensitive disulfide bond. The GO/prodrug nanohybrids (GOPN) was prepared via the hydrophobic and π-π interaction between the hydrophobic block of PCL-SS-DOX and the aromatic ring of GO. The redox-sensitive PEG-PCL-SS-DOX molecules integrate the anticancer drug and dispersant/stabilizing agent together into GO. In other words, prodrug molecules act as the dispersant/stabilizing agent and simultaneously provide the redox-sensitive property which ensures the effective release of the anticancer drug in tumor site demonstrated by the in vitro release results. The in vitro cell cytotoxicity showed that the GOPN could significantly enhance DOX accumulation in A549 and B16 cells and effectively enhance the anticancer activity. In vivo antitumor and histological examination results suggested that GOPN could reduce the DOX systemic toxicity with remarkable inhibition of tumor growth. The prepared GOPN could solve the incomplete and slow release problem of the previously reported GO-based drug delivery system, and resulting in the desirable anticancer effect of DOX. Therefore, the present constructed GOPN bring a new opportunity for effective cancer therapy.