Targeted delivery of novel Au(I)-based AIEgen via inactivated cancer cells for trimodal chemo-radio-immunotherapy and vaccination against advanced tumor

Duo，Yanhong1,2,3,4; Chen，Zide1,5; Li，Kuming6; Yang，Yaoqiang1,3; Wang，Hao3; Hu，Jiliang3; Luo，Guanghong1,2,3

2023-08-01

10.1016/j.nantod.2023.101920

Nano Today   Impact Factor & Quartile

1748-0132

1878-044X

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.

Aggregation-induced emission Immunogenic cell death Immunotherapy Inactivated cancer cells Radiotherapy Vaccination

SCI

English

First ; Corresponding

Basic and Applied Basic Research Foundation of Guangdong Province[2022A1515110534];National Natural Science Foundation of China[82102904];Medical Science and Technology Foundation of Guangdong Province[A2022122];Science, Technology and Innovation Commission of Shenzhen Municipality[JCYJ20190807144605514];Science, Technology and Innovation Commission of Shenzhen Municipality[JCYJ20190808154213097];Science, Technology and Innovation Commission of Shenzhen Municipality[JCYJ20210324113405014];Science, Technology and Innovation Commission of Shenzhen Municipality[JCYJ20210324113810029];

Chemistry ; Science & Technology - Other Topics ; Materials Science

Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:001041548300001

ELSEVIER SCI LTD

2-s2.0-85164223753

Scopus

1.Department of Radiation Oncology,Shenzhen People's Hospital (The Second Clinical Medical College,Jinan University; The First Affiliated Hospital,Southern University of Science and Technology),Shenzhen,Guangdong,518020,China
2.Department of Microbiology,Tumor and Cell Biology (MTC),Karolinska Institutet,Stockholm,Sweden
3.Department of neurosurgery,Shenzhen People's Hospital (The Second Clinical Medical College of Jinan University,The First Affiliated Hospital of the Southern University of Science and Technology),Shenzhen,Guangdong,518020,China
4.Key Lab for New Drug Research of TCM,Research Institute of Tsinghua University in Shenzhen,Shenzhen,Guangdong,518057,China
5.Department of Interventional Radiology,Guangdong Provincial People's Hospital,Guangdong Academy of Medical Sciences,Guangzhou,Guangdong,510080,China
6.Department of Oral and Maxillofacial Surgery,Shenzhen People's Hospital (The Second Clinical Medical College,Jinan University,Southern University of Science and Technology),Shenzhen,Guangdong,518020,China

Duo，Yanhong,Chen，Zide,Li，Kuming,et al. Targeted delivery of novel Au(I)-based AIEgen via inactivated cancer cells for trimodal chemo-radio-immunotherapy and vaccination against advanced tumor[J]. Nano Today,2023,51.

Duo，Yanhong.,Chen，Zide.,Li，Kuming.,Yang，Yaoqiang.,Wang，Hao.,...&Luo，Guanghong.(2023).Targeted delivery of novel Au(I)-based AIEgen via inactivated cancer cells for trimodal chemo-radio-immunotherapy and vaccination against advanced tumor.Nano Today,51.

Duo，Yanhong,et al."Targeted delivery of novel Au(I)-based AIEgen via inactivated cancer cells for trimodal chemo-radio-immunotherapy and vaccination against advanced tumor".Nano Today 51(2023).