Nuclear-Targeted Nanostrategy Regulates Spatiotemporal Communication for Dual Antitumor Immunity

Area of Science:

• Oncology
• Immunology
• Nanotechnology
• Biomedical Engineering

Background:

• Tumor cells and immune cells communicate, influencing tumor progression.
• Current therapies often focus on suppressing negative tumor-immune interactions (e.g., PD-L1/PD-1).
• Enhancing positive tumor-immune communication remains a significant challenge.

Purpose of the Study:

• To develop a nuclear-targeted photodynamic nanostrategy for improving positive intercellular communication.
• To activate dual antitumor immunity (innate and adaptive) for enhanced cancer treatment.
• To establish spatiotemporal control over immune responses within the tumor microenvironment.

Main Methods:

• Design of mSiO2-Ion@Ce6-NLS nanoparticles loaded with photosensitizer (Ce6) and modified with ionic liquid silicon (Ion) and nuclear localization signal peptide (NLS).
• Utilizing nuclear-targeted photodynamic therapy (nPDT) to induce immunogenic cell death and DNA release.
• Investigating the activation of macrophages via stimulator of interferon gene signaling and dendritic cells via "eat me" signals.

Main Results:

• nPDT facilitated the release of damaged double-stranded DNA from tumor cells.
• Macrophage activation via stimulator of interferon gene signaling and dendritic cell activation were observed.
• Recruitment of CD8+ T-cells and reshaping of the tumor immune microenvironment were achieved.
• Long-term immune memory and significant inhibition of tumor growth and recurrence were demonstrated.

Conclusions:

• The developed nuclear-targeted photodynamic nanostrategy effectively enhances positive tumor-immune communication.
• This approach successfully activates dual antitumor immunity, leading to potent anti-cancer effects.
• The strategy holds promise for overcoming challenges in cancer immunotherapy and preventing tumor recurrence.