Design of a Wobble-Scheme Heterojunction for Catalytic Cancer Therapy

Area of Science:

• Biomedical Engineering
• Materials Science
• Nanotechnology

Background:

• Nanocatalytic medicine offers a promising avenue for tumor therapy.
• Photocatalytic nanoscale heterostructures are crucial for designing effective nanocatalysts.
• The tumor microenvironment (TME) presents unique challenges and opportunities for therapeutic interventions.

Purpose of the Study:

• To design and investigate a novel organic-inorganic core-shell nanoreactor (Bi@COF) as a dynamic heterojunction for tumor therapy.
• To explore the TME-responsive mechanism of COF tautomerization for regulating nanocatalytic activity.
• To establish an intracellular self-sufficient reactive oxygen species (ROS) system for synergistic photothermal and photodynamic therapy.

Main Methods:

• Fabrication of a Bi@COF core-shell nanoreactor with a wobble-scheme heterojunction.
• Investigation of COF shell's reversible enolimine-ketoenamine tautomerization in acidic TME.
• Utilizing near-infrared (NIR) irradiation to trigger H2O2 generation and photothermal effects.
• Experimental and theoretical analyses (e.g., band alignment, charge transfer) to understand the catalytic mechanism.
• Assessment of ROS generation, intracellular redox homeostasis disruption, and cancer cell apoptosis.

Main Results:

• The Bi@COF nanoreactor exhibits TME responsiveness, dynamically switching between reduction/oxidation (RP/OP) junctions via COF tautomerization.
• NIR irradiation of the reconfigured heterojunction efficiently catalyzes in situ H2O2 generation, amplified by photothermal effects.
• COF tautomerization reconstructs the conjugated framework, modulates band alignment, and facilitates proton-coupled electron transfer (PCET) for enhanced H2O2 production.
• The integrated system effectively disrupts intracellular redox homeostasis and induces cancer cell apoptosis.

Conclusions:

• The wobble-scheme heterojunction-mediated ROS self-supply system offers a novel strategy for synergistic photothermal and photodynamic tumor therapy.
• Dynamic regulation of heterojunctions through TME-responsive mechanisms holds significant promise for advanced nanocatalytic medicine.
• This approach provides a new paradigm for developing intelligent nanoreactors for cancer treatment.