Developing Single-Atomic Manganese Nanozymes for Synergistic Mild Photothermal/Multienzymatic Therapy.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Osteosarcoma treatment requires advanced therapies with enhanced efficacy.
• Synergistic approaches combining photothermal and enzymatic activities are highly desirable.
• Developing nanozymes with multiple catalytic functions is crucial for overcoming treatment resistance.

Purpose of the Study:

• To develop single-atom nanozymes (SANs) for synergistic mild photothermal and multienzymatic therapy against osteosarcoma.
• To investigate the therapeutic mechanisms of Mn-SANs in disrupting cancer cell redox homeostasis and overcoming resistance.
• To evaluate the potential of Mn-SANs as an efficient treatment strategy for osteosarcoma.

Main Methods:

• Fabrication of single-atom nanozymes (SANs) with Mn sites on nitrogen-doped carbon nanosheets (Mn-SANs).
• Evaluation of NIR-II-triggered photothermal performance of Mn-SANs.
• Assessment of multienzyme activities including catalase (CAT)-like, oxidase (OXD)-like, and glutathione oxidase (GSHOx)-like functions.
• Investigation of Mn-SANs' effects on reactive oxygen species (ROS) production, glutathione (GSH) consumption, lipid peroxide (LPO) accumulation, and heat shock protein (HSP) degradation in osteosarcoma cells.

Main Results:

• Mn-SANs exhibited excellent NIR-II photothermal conversion efficiency.
• Mn-SANs demonstrated potent CAT-like, OXD-like, and GSHOx-like activities, leading to O2 generation, superoxide anion radical (•O2-) production, and GSH depletion.
• Mn-SANs effectively inhibited GPX4 expression and promoted LPO accumulation, inducing oxidative stress and disrupting redox homeostasis.
• The combined therapy significantly impaired osteosarcoma cells, including those resistant to mild photothermal therapy, by degrading HSPs.

Conclusions:

• Mn-SANs offer a promising synergistic therapy for osteosarcoma by combining mild photothermal and multienzymatic actions.
• The developed Mn-SANs effectively induce cancer cell death through oxidative stress, redox homeostasis disruption, and enhanced therapeutic effects.
• This nanozyme-based strategy presents a novel and efficient approach for osteosarcoma treatment, addressing challenges of hypoxia and therapeutic resistance.