Core Viewpoint - The article discusses a novel approach to enhance CD47 blockade therapy for cancer treatment by utilizing biomineralized nanoparticles that facilitate phagocytosis and mitochondrial DNA sensing, leading to improved therapeutic outcomes [2][5]. Group 1: Research Background - Antigen-presenting cells (APCs) mediate the phagocytosis of cancer cells and initiate antigen presentation through sensing mitochondrial DNA (mtDNA), which is a critical mechanism in CD47 blockade therapy [2]. - Current strategies targeting CD47 often lack regulation of mtDNA sensing, limiting their effectiveness [2]. Group 2: Research Findings - The study developed biomineralized nanoparticles ZnCO₃@BSA/siCD47 that enhance CD47 blockade therapy by promoting APC phagocytosis and mtDNA sensing, resulting in significant tumor growth inhibition [2][5]. - The nanoparticles are designed to balance the stable encapsulation of siRNA with efficient intracellular release, achieving effective CD47 silencing and Zn²⁺ overload [5][6]. - In colorectal cancer and melanoma models, ZnCO₃@BSA/siCD47 restored APC function, increased T cell infiltration, and achieved a tumor growth inhibition rate of 93% [5][6]. Group 3: Mechanism of Action - The strategy involves Zn²⁺ overload to enhance phagocytosis and STING activation, while the pH-responsive ZnCO₃@BSA matrix ensures synchronized delivery of Zn²⁺ and siRNA [6]. - The treatment induces CD47 knockdown, calreticulin exposure, and mtDNA release, which are crucial for effective immune response [6].