Programmed Cascade Polydopamine Nanoclusters for Pyroptosis-Based Tumor Immunotherapy

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Immunotherapy

Background:

• Pyroptosis is a crucial inflammatory cell death pathway for anti-tumor immunity.
• Efficiently inducing pyroptosis in tumor cells remains a challenge for cancer immunotherapy.

Purpose of the Study:

• To develop a pH-responsive nanoplatform for enhanced phototherapy-induced pyroptosis.
• To amplify anti-tumor immunity by modulating the tumor microenvironment.

Main Methods:

• Design of a pH-responsive polydopamine nanocluster (R-P@PDA-GC) encapsulating oxygen donors, photosensitizers, and anti-cancer agents.
• Utilizing a two-input programmed cascade therapy involving pH-responsiveness and dual-wavelength irradiation.
• Assessment of pyroptosis induction, immune cell modulation, and anti-tumor effects in the tumor microenvironment (TME).

Main Results:

• The nanoplatform effectively delivered oxygen, mitigated tumor hypoxia, and enhanced heat resistance.
• Dual-input irradiation triggered significant reactive oxygen species production, inducing pyroptosis via the Caspase-1/GSDMD pathway.
• Enhanced maturation of dendritic cells, increased infiltration of CD8+ T and NK cells, and reduced Treg cells were observed, amplifying anti-tumor immunity.

Conclusions:

• The developed nanoplatform shows promise for augmenting phototherapy-induced pyroptosis and boosting anti-tumor immunotherapy.
• This programmed cascade therapy offers a novel strategy for overcoming challenges in precise tumor cell pyroptosis induction.
• The approach effectively reprograms the tumor microenvironment to enhance immune responses against cancer.