Targeted delivery of novel Au(I)-based AIEgen via inactivated cancer cells for trimodal chemo-radio-immunotherapy and vaccination against advanced tumor
Yanhong Duo, Zide Chen, Kunming Li, Yaoqiang Yang, Hao Wang, Jiliang Hu, Guanghong Luo
Abstract
Radiotherapy-induced immunogenic cell death (ICD) has been proven to be an effective strategy for evoking immunotherapeutic effects against advanced tumors. Components from the dead cancer cells have been shown to serve as natural drug carriers and have also demonstrated great advantages in tumor-targeted delivery and immune activation. Herein, we constructed an inactivated cancer cells vector for novel Au(I)-based AIEgen (complex 1) AIEgen to augment the targeted delivery of AIEgen toward tumor tissue. More importantly, the AIEgen exerted toxicity against cancer cells and mainly localized within the endoplasmic reticulum and part of lysosome. Upon X-ray irradiation, a synergistic therapeutic effects of trimodal chemo-radio-immunotherapy was achieved, where the AIEgen effectively induced ICD by triggering ROS production and DNA damage. Further, it stimulated a robust systemic antitumor immune response via the upregulation of various cytokines and the activation of the cGAS-STING pathway, thereby activating innate and adaptive immunity in melanoma tumor model. Furthermore, in vivo, the ICD-inducing immunogenicity of AIEgen combined with radiotherapy served as a cancer cell vaccine strategy to inhibit tumorigenesis. This approach engineered strategy based on dead cancer cells vector serves as a bridge combining AIEgen, chemotherapy, radiotherapy, and immunotherapy, and provides a simple and effective scheme for trimodal chemo-radio-immunotherapy and improving therapeutic effects.