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Supramolecular Nanozyme System Based on Polydopamine and Polyoxometalate for Photothermal-Enhanced Multienzyme
Zhengchao Zhang1, Dejun Ding1, Jinxiang Liu2,3
1College of Pharmacy, Weifang Medical University, Weifang, Shandong 261053, P. R. China.
Abstract:
The advent of enzyme-facilitated cascade events in which endogenous substrates within the human body are used to generate reactive oxygen species (ROS) has spawned novel cancer treatment possibilities. In this study, a supramolecular cascade catalytic nanozyme system was successfully developed, exhibiting photothermal-enhanced multienzyme cascade catalytic and glutathione (GSH) depletion activities and ultimately triggering the apoptosis-ferroptosis synergistic tumor therapy. The nanozyme system was fabricated using β-cyclodextrin-functionalized polydopamine (PDA) as the substrate, which was then entangled with polyoxometalate (POM) via electrostatic forces and assembled with adamantane-grafted hyaluronic acid and glucose oxidase (GOx) via host-guest supramolecular interaction for tumor targeting and GOx loading. The catalytic function of GOx facilitates the conversion of glucose to H2O2 and gluconic acid. In turn, this process affirms the propitious generation of hydroxyl radical (•OH) through the POM-mediated cascade catalysis. Additionally, the POM species actively deplete the intracellular GSH pool, initiating a cascade catalytic tumor therapy. In addition, the PDA-POM-mediated photothermal hyperthermia boosted the cascade catalytic effect and increased ROS production. This confers considerable promise for photothermal therapy (PTT)/nanocatalytic cancer therapy on supramolecular nanozyme systems. The in vitro and in vivo antitumor efficacy studies demonstrated that the supramolecular cascade catalytic nanozyme system was effective at reducing tumor development while maintaining an acceptable level of biocompatibility. Henceforth, this study is to widen the scope of cascade catalytic nanoenzyme production using supramolecular techniques, as well as endeavor to delineate a prospective pathway for the application of PTT-enhanced nanocatalytic tumor therapy.
Insights
Researchers developed a novel nanozyme system for cancer therapy. This system uses photothermal enhancement and cascade catalysis to trigger apoptosis and ferroptosis, effectively reducing tumors with good biocompatibility.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapy
Background:
- Enzyme-facilitated cascade reactions offer new cancer treatment avenues by generating reactive oxygen species (ROS) from endogenous substrates.
- Developing sophisticated nanozyme systems is crucial for advancing synergistic tumor therapies.
Purpose of the Study:
- To fabricate a supramolecular cascade catalytic nanozyme system with photothermal-enhanced activity.
- To investigate the nanozyme's glutathione (GSH) depletion and ROS generation capabilities.
- To evaluate the synergistic apoptosis-ferroptosis tumor therapy efficacy in vitro and in vivo.
Main Methods:
- Fabrication of a nanozyme system using β-cyclodextrin-functionalized polydopamine (PDA), polyoxometalate (POM), adamantane-grafted hyaluronic acid, and glucose oxidase (GOx).
- Utilizing host-guest supramolecular interactions for tumor targeting and GOx loading.
- Employing photothermal hyperthermia to enhance cascade catalysis and ROS production.
Main Results:
- The nanozyme system successfully converted glucose to H2O2 and gluconic acid, generating hydroxyl radicals (•OH) via POM-mediated cascade catalysis.
- POM effectively depleted intracellular GSH, initiating cascade catalytic therapy.
- Photothermal hyperthermia significantly boosted catalytic activity and ROS generation.
- In vitro and in vivo studies confirmed significant tumor reduction with good biocompatibility.
Conclusions:
- The developed supramolecular nanozyme system demonstrates potent synergistic apoptosis-ferroptosis tumor therapy.
- Photothermal enhancement amplifies the nanozyme's catalytic efficiency and ROS production.
- This work expands the scope of supramolecular nanozyme design for PTT-enhanced nanocatalytic cancer therapy.
