Multifunctional Nanoplatform for Synergistic Cancer Therapy via Enhanced Immunogenic Cell Death and Immune Modulation

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Research

Background:

• Cancer remains a significant global health threat, necessitating advanced therapeutic strategies.
• Current treatments often face challenges like limited efficacy and tumor microenvironment suppression.

Purpose of the Study:

• To develop a multifunctional nanoplatform (ZPMTH) for cancer therapy.
• To leverage the nanoplatform for activating immunogenic cell death (ICD) and immune responses.

Main Methods:

• Fabrication of ZnO2@PtMn@Tir@HA (ZPMTH) nanoplatform.
• Utilizing ZPMTH as a nanozyme to generate reactive oxygen species (ROS) for tumor cell apoptosis.
• Investigating ZPMTH's role in activating the cGAS-STING pathway and promoting dendritic cell maturation.
• Evaluating ZPMTH's therapeutic efficacy in vitro and in vivo.

Main Results:

• ZPMTH effectively produced intratumoral ROS (•OH and 1O2), inducing cancer cell death and ICD.
• The nanoplatform activated the cGAS-STING pathway, enhancing anti-tumor immunity.
• Tirabrutinib (Tir) component suppressed Bruton's tyrosine kinase (BTK), alleviating the immunosuppressive tumor microenvironment.
• ZPMTH promoted dendritic cell maturation and demonstrated significant tumor growth inhibition in primary and contralateral models.

Conclusions:

• ZPMTH serves as a potent nanozyme and ICD nanoinducer for synergistic cancer therapy.
• The nanoplatform effectively stimulates anti-tumor immunity and overcomes tumor microenvironment suppression.
• ZPMTH presents a promising strategy for advancing cancer immunotherapy.