High-Entropy-Engineered Nanoinducer for Spatiotemporally Programmed PANoptosis and NIR-Amplified Cancer Immunotherapy

Area of Science:

• Biomedical Engineering
• Immunology
• Materials Science

Background:

• PANoptosis (programmed all-cause cell death) is a promising strategy for enhancing antitumor immunity.
• Current methods for inducing PANoptosis in cancer therapy face challenges in spatiotemporal control and reactive oxygen species (ROS) generation, leading to off-target effects.

Purpose of the Study:

• To develop a novel nanoinducer for spatiotemporally controlled PANoptosis-specific cancer cell death.
• To enhance antitumor immune responses and overcome limitations of existing cancer immunotherapies.

Main Methods:

• Construction of a PANoptosis nanoinducer using atomically dispersed high-entropy metal sites (HENA@PEG).
• Utilizing near-infrared (NIR) light for amplified, spatiotemporally controlled activation.
• Integrating nanozyme-mediated photothermal therapy (PTT) for enhanced catalytic activity and tumor ablation.
• Employing pH-gated control for precise ROS generation.

Main Results:

• The HENA@PEG nanoinducer demonstrated boosted catalytic efficiency and precise ROS generation.
• NIR-amplified PTT and catalytic activation synergistically induced tumor-site-adaptive biocatalysis and PANoptosis.
• Effective promotion of dendritic cell maturation and cytotoxic T-cell activation observed.
• Significant suppression of 4T1 tumor progression in vivo.

Conclusions:

• A high-entropy-engineered nanoinducer enables precise, spatiotemporal induction of PANoptosis for cancer immunotherapy.
• This approach overcomes limitations of nonspecific cell death and immune evasion.
• Represents a promising strategy for developing more effective and targeted cancer treatments.