Celastrol Loaded PEGylated Nanographene Oxide for Highly Efficient Synergistic Chemo/Photothermal Therapy

Aim: The main aim of this study is to improve the solubility, reduce side effects and increase the therapeutic efficacy of CSL by using functionalized graphene oxide as a carrier, to fulfill chemo-photothermal therapy. Background: Celastrol (CSL), which is extracted from the traditional Chinese medicinal plant Tripterygium wilfordii, has reported significant antitumor activity in vitro and in vivo cancer models. However, disadvantages with regard to solubility, short plasma half-life and toxicity hinder its use in pharmaceutical application. Nanocarrier delivery system could be employed to improve the biochemical and pharmacokinetic performance of CSL. Among numerous nanocarriers, graphene oxide is one of the most promising nanocarriers due to its intrinsic physical and chemical properties and good biocompatibility. Objective: Here, we employed a PEGylated reduced nanographene oxide CSL complex (nrGO-PEG/CSL) as a new drug delivery system to achieve highly efficient synergistic chemo/photothermal therapy. Methods: A functionalized nrGO-PEG was synthesized and the loading capacity of CSL, photothermal effect and release efficiency under different pH and NIR irradiation were measured in the first stage of work. In vitro and in vivo anticancer effects of prepared nrGO-PEG/CSL complex were evaluated on 4T1 cells and 4T1 tumor-bearing mice, respectively, with the association of NIR laser irradiation. Results: The functionalized nrGO-PEG exhibited excellent drug loading capacity of CSL (20.76 mg/mg GO) and photothermal effect (similar to 3.0 -fold increment over unreduced nGO-PEG). Loaded CSL could be efficiently released from nrGO-PEG/CSL complex by NIR irradiation in vitro. In vivo study performed on 4T1 tumor-bearing mice proved that nrGO-PEG/CSL with NIR laser irradiation shows superior anticancer effects. Conclusion: The experimental data demonstrated that the nrGO-PEG/CSL-mediated chemo/photothermal combination therapy was more cytotoxic to cancer cells than only chemotherapy or photothermal treatment, reducing the occurrence of tumor metastasis. Therefore, nrGO-PEG/CSL-mediated chemo/photothermal is expected to be a promising treatment for synergistic cancer therapy.