Adenosine Triphosphate Disodium Hydrate

Amidst the therapeutic quandaries associated with triple-negative breast cancer (TNBC), an aggressive malignancy distinguished by its immune resistance and limited treatment avenues, the urgent need for innovative solutions is underscored. To conquer the dilemma, we present a groundbreaking approach that ingeniously employs DNA-fragments-containing exosomes (DNA-Exo) and the concept of "biological logic-gates" to achieve precise homing and controlled selective activation of ferroptosis and stimulator interferon genes (STING) pathways. Leveraging insights from our previous research, a nano-Trojan-horse, Fe⁰@HMON@DNA-Exo, is engineered via in situ Fe⁰ synthesis within the glutathione (GSH)-responsiveness degradable hollow mesoporous organosilica nanoparticles (HMON) and subsequently enveloped in DNA-Exo derived from 7-ethyl-10-hydroxycamptothecin (SN38)-treated 4T1 cells. Emphasizing the precision of our approach, the DNA-Exo ensures specific 'homing' to TNBC cells, rendering a targeted delivery mechanism. Concurrently, the concept of "biological logic-gates" is employed to dictate a meticulous and selective activation of STING in antigen-presenting cells (APCs) under OR logic-gating with robust immune response and Fe⁰-based ferroptosis in TNBC cells under AND logic-gating with reactive oxygen species (ROS) storm generation. In essence, our strategy exhibits great potential in transforming the "immunologically cold" nature of TNBC, enabling precise control over cellular responses, illuminating a promising therapeutic paradigm that is comprehensive and productive in pursuing precision oncology and paving the way for personalized TNBC therapies.

The epithelial-mesenchymal transition (EMT), tumor stroma and local metabolic alterations cooperate to establish a unique tumor microenvironment (TME) that fosters tumor progression and metastasis. To tackle this challenge, a precision intelligent nanomissile named HA@AT-Pd has been designed for dual-pronged cancer-associated fibroblast (CAF) transformation and tumor cell elimination. It is observed that HA@AT-Pd inhibits the production of cancer stem cells (CSCs) by blocking the TGF-β/Smad signaling pathway-mediated EMT and reversing activated CAFs to quiescence. Notably, HA@AT-Pd induces energy depletion in breast cancer cells through simultaneously suppressing cellular oxidative phosphorylation and glycolysis. The inhibition of glycolysis results in reduced lactic acid production, thereby converting an immunosuppressive TME into an immune-activating environment. Furthermore, the photothermal effect generated by HA@AT-Pd evokes immunogenic cell death, which can further enhance the anti-tumor immune response. Overall, this multifunctional combination strategy unveils potential therapeutic avenues to inhibit tumor progression and metastasis.