Nanoparticle Metalloimmunotherapy for Cancer Eradication: Comprehensive Evaluation From Mice to NHPs

Nutritional metal ions play an essential role in various immune processes and offer opportunities for a new class of immunotherapy, termed "Metalloimmunotherapy." The STING pathway is a critical mediator of immune activation. However, efficient systemic delivery of STING agonists remains a challenge. Here, we present the development of a novel lipid nanoparticle-based platform for the systemic delivery of cyclic dinucleotide (CDN) STING agonists and Mn²⁺, achieving potent anti-tumor efficacy and favorable pharmaceutical properties across multiple preclinical models.