Dual-Heterojunctions with Reversibly Photoactivated Structure Shift Alternately Decode Photocatalytic H₂ Burst and...

Area of Science:

• Biomedical Engineering
• Materials Science
• Oncology

Background:

• Cancer therapies, including reactive oxygen species (ROS) treatments, often face challenges with acquired resistance after prolonged use.
• Concurrent hydrogen (H2)/ROS therapy shows promise but is limited by the mutual interference between H2 and ROS, reducing overall efficacy.

Purpose of the Study:

• To develop an advanced therapeutic strategy that overcomes cancer resistance by decoupling H2 and ROS generation.
• To investigate the potential of g-C3N4-based dual-heterojunctions for temporally controlled, alternate H2/ROS therapy.

Main Methods:

• Fabrication of g-C3N4-based dual-heterojunctions: N-doped carbon nanoribbons (N-CNB)/g-C3N4 for photocatalytic H2 evolution and Au@Pd nanoparticles/g-C3N4 for bioenzyme-like ROS generation.
• Utilizing near-infrared (NIR) light to trigger H2 evolution (NIR on) and ROS generation (NIR off) via reversible photoirradiation-induced structural shifts.
• Evaluating the therapeutic efficacy in suppressing common and Sorafenib-induced resistant liver cancer models.

Main Results:

• The N-CNB/g-C3N4 heterojunctions effectively utilized NIR light for H2 evolution, while Au@Pd/g-C3N4 heterojunctions catalyzed ROS production.
• Alternate H2/ROS therapy demonstrated temporal controllability under NIR irradiation, decoupling the reactive species.
• This therapy significantly enhanced anti-tumor immune cell infiltration (CTLs, Th17), reduced immunosuppressive cells (exhausted CD8+ T cells, Tregs), and downregulated resistance markers (PARP, EpCAM, CD133).

Conclusions:

• Alternate H2/ROS therapy effectively suppresses both common and Sorafenib-resistant liver cancer by activating robust immune responses.
• The developed g-C3N4-based dual-heterojunctions offer a novel platform for temporal control in cancer therapy, overcoming resistance mechanisms.
• This strategy provides valuable insights into mitigating cancer resistance and enhancing immunotherapeutic outcomes.