A pH-sensitive supramolecular nanosystem with chlorin e6 and triptolide co-delivery for chemo-photodynamic combination therapy

The combination of Ce6,an acknowledged photosensitizer,and TPL,a natural anticancer agent,has been demonstrated as a useful strategy to reinforce the tumor growth suppression,as well as decrease the systemic side effects compared with their monotherapy.However,in view of the optimal chemo-photodynamic combination efficiency,there is still short of the feasible nanovehicle to steadily co-deliver Ce6 and TPL,and stimuli-responsively burst release drugs in tumor site.Herein,we described the synergistic antitumor performance of a pH-sensitive supramolecular nanosystem,mediated by the host–guest complexing betweenβ-CD and acid pH-responsive amphiphilic co-polymer mPEG-PBAE-mPEG,showing the shell–core structural micelles with the tightβ-CD layer coating.Both Ce6 and TPLwere facilely co-loaded into the spherical supramolecular NPs(TPL+Ce6/NPs)by one-step nanoprecipitation method,with an ideal particle size(156.0 nm),acid pH-responsive drug release profile,and enhanced cellular internalization capacity.In view of the combination benefit of photodynamic therapy and chemotherapy,as well as co-encapsulation in the fabricated pH-sensitive supramolecular NPs,TPL+Ce6/NPs exhibited significant efficacy to suppress cellular proliferation,boost ROS level,lower MMP,and promote cellular apoptosis in vitro.Particularly,fluorescence imaging revealed that TPL+Ce6/NPs preferentially accumulated in the tumor tissue area,with higher intensity than that of free Ce6.As expected,upon 650-nm laser irradiation,TPL+Ce6/NPs exhibited a cascade of amplified synergistic chemo-photodynamic therapeutic benefits to suppress tumor progression in both hepatoma H22 tumor-bearingmice and B16 tumor-bearingmice.More importantly,lower systemic toxicitywas found in the tumor-bearingmice treated with TPL+Ce6/NPs.Overall,the designed supramolecular TPL+Ce6/NPs provided a promising alternative approach for chemo-photodynamic therapy in tumor treatment.