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Tuesday, April 16, 2024

Focused supply of novel Au(I)-based AIEgen by way of inactivated most cancers cells for trimodal chemo-radio-immunotherapy and vaccination towards superior tumor


Radiotherapy-induced immunogenic cell loss of life (ICD) has been confirmed to be an efficient technique for evoking immunotherapeutic results towards superior tumors. Elements from the lifeless most cancers cells have been proven to function pure drug carriers and have additionally demonstrated nice benefits in tumor-targeted supply and immune activation. Herein, we constructed an inactivated most cancers cells vector for novel Au(I)-based AIEgen (advanced 1) AIEgen to enhance the focused supply of AIEgen towards tumor tissue. Extra importantly, the AIEgen exerted toxicity towards most cancers cells and primarily localized inside the endoplasmic reticulum and a part of lysosome. Upon X-ray irradiation, a synergistic therapeutic results of trimodal chemo-radio-immunotherapy was achieved, the place the AIEgen successfully induced ICD by triggering ROS manufacturing and DNA harm. Additional, it stimulated a sturdy systemic antitumor immune response by way of the upregulation of assorted cytokines and the activation of the cGAS-STING pathway, thereby activating innate and adaptive immunity in melanoma tumor mannequin. Moreover, in vivo, the ICD-inducing immunogenicity of AIEgen mixed with radiotherapy served as a most cancers cell vaccine technique to inhibit tumorigenesis. This strategy engineered technique primarily based on lifeless most cancers cells vector serves as a bridge combining AIEgen, chemotherapy, radiotherapy, and immunotherapy, and supplies a easy and efficient scheme for trimodal chemo-radio-immunotherapy and enhancing therapeutic results.

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