Traditional
cancer therapies no longer meet the current demand for
cancer precision
therapy and personalized treatment and it's essential to develop new therapeutic modalities as well as to investigate new combination anti-
tumor mechanisms. Therefore, amphiphilic
prodrug polymer chains linking methoxy poly(
ethylene glycol) (
mPEG) and
cinnamaldehyde (CA) with
adipic acid dihydrazide (ADH) as the pH-responsive center were designed and synthesized, which could self-assemble into PAC
micelles in aqueous
solution. A supramolecular
hydrogel was formed based on the host-guest interaction between α-
cyclodextrin (α-CD) and PAC
micelles.
Polyetherimide (PEI) modified
copper manganese sulfide nanoenzyme catalysts (PCMS NPs) were prepared by a solvothermal method, which could be uniformly dispersed in the
hydrogel to form a composite supramolecular
hydrogel (PCMS@PAC/α-CD Gel). Under an acidic
tumor environment, pH-responsive
hydrazone bonds were broken, resulting in the slow release of CA and the amplification of
hydrogen peroxide (H2O2) levels. PCMS NPs exerted
peroxidase (POD)-like activity and
catalase (CAT)-like activity, which could convert H2O2 into
hydroxyl radicals (˙OH) and
oxygen (O2) to alleviate intra-tumor hypoxia and induce apoptosis, while exerting
glutathione oxidase (GPX)-like activity to consume
glutathione (GSH) to further enhance the effect of chemodynamic
therapy (CDT). Under near-infrared light (NIR) irradiation, PCMS NPs exhibited an excellent photothermal conversion performance, which could rapidly increase the temperature of
tumor cells to above 42 °C for
photothermal therapy (PTT) and convert O2 to a
superoxide anion (˙O2-) by exerting
oxidase (OXD)-like activity for
photodynamic therapy (
PDT). It was demonstrated by in vitro and in vivo experiments that the PCMS@PAC/α-CD Gel was highly cytotoxic to
cancer cells and could effectively inhibit
tumor growth, indicating the potential for applications in the fields of biomedicine and
smart materials.