Zwitterionic Nanoplatform-Mediated Photopyroptosis for Abscopal Effect-Enhanced Cancer Immunotherapy

Area of Science:

• Oncology
• Immunology
• Materials Science

Background:

• Cancer immunotherapy faces challenges with weak systemic immunity, particularly against distant tumors.
• Pyroptosis, a cell death method, shows promise but lacks controlled activation and carries risks of inflammation.
• Photodynamically induced pyroptosis offers precise, localized activation to overcome these limitations.

Purpose of the Study:

• To develop a nanoplatform for controlled photopyroptosis induction within tumors.
• To leverage photopyroptosis for enhanced systemic anti-tumor immunity and abscopal effects.
• To integrate imaging guidance with photopyroptosis for precise cancer treatment.

Main Methods:

• Zwitterionic nanogels were developed to deliver verteporfin, a photosensitizer.
• The nanogels were designed for mitochondrial localization and near-infrared-triggered photopyroptosis.
• Intrinsic fluorescence of verteporfin was used for imaging-guided irradiation.

Main Results:

• Zwitterionic nanogels improved verteporfin's solubility, pharmacokinetics, and tumor accumulation.
• Near-infrared activation induced gasdermin-mediated pyroptosis, leading to immunogenic cell death.
• The treatment activated systemic anti-tumor immune responses, demonstrating an abscopal effect.

Conclusions:

• Mitochondria-targeted zwitterionic nanogels enable imaging-guided photopyroptosis.
• This approach enhances local tumor cell death and promotes systemic anti-tumor immunity.
• The integrated platform shows potential for abscopal effect-enhanced cancer suppression.