DataVXAdvanced SciencePaper
journal article·2024-01Open access

Cancer Nanobombs Delivering Artoxplatin with a Polyigniter Bearing Hydrophobic Ferrocene Units Upregulate PD‐L1 Expression and Stimulate Stronger Anticancer Immunity

Yongchao Gao, Hanchen Zhang, Lin Tang, Feifei Li, Li Yang, Haihua Xiao, Johannes Karges, Weihua Huang, Wei Zhang, Chaoyong Liu

Advanced Science· Volume 11· Issue 4
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Source abstract

Abstract

Abstract Poor immunogenicity seriously hampers the broader implementation of antitumor immunotherapy. Enhanced immunogenicity capable of achieving greater antitumor immunity is urgently required. Here, a novel polymer that contains hydrophobic ferrocene (Fc) units and thioketal bonds in the main chain, which further delivered a prodrug of oxaliplatin and artesunate, i.e., Artoxplatin, to cancer cells is described. This polymer with Fc units in the nanoparticle can work as a polyigniter to spark the peroxide bonds in Artoxplatin and generate abundant reactive oxygen species (ROS) to kill cancers as nanobombig for cancer therapy. Moreover, ROS can trigger the breakdown of thioketal bonds in the polymer, resulting in the biodegradation of the polymer. Importantly, nanobombig can facilitate the maturation of dendritic cells and promote the activation of antitumor immunity, through the enhanced immunogenic cell death effect by ROS generated in situ. Furthermore, metabolomics analysis reveals a decrease in glutamine in nanobombig‐treated cancer cells, resulting in the upregulation of programmed death ligand 1 (PD‐L1). Consequently, it is further demonstrated enhanced tumor inhibitory effects when using nanobombig combined with anti‐PD‐L1 therapy. Overall, the nanosystem offers a rational design of an efficient chemo‐immunotherapy regimen to promote antitumor immunity by improving tumor immunogenicity, addressing the key challenges cancer immunotherapy faced.
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Research context

PolymersNanomaterials

OpenAlex topics: Nanoplatforms for cancer theranostics · Peptidase Inhibition and Analysis · MXene and MAX Phase Materials

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Clinical Pharmacology Xiangya Hospital Central South University 87 Xiangya Road Changsha 410008 P. R. China

Institute of Clinical Pharmacology Central South University Hunan Key Laboratory of Pharmacogenetics 110 Xiangya Road Changsha 410078 P. R. China

Engineering Research Center of Applied Technology of Pharmacogenomics Ministry of Education 110 Xiangya Road Changsha 410078 P. R. China

National Clinical Research Center for Geriatric Disorders 87 Xiangya Road Changsha Hunan 410008 P. R. China

Beijing National Laboratory for Molecular Sciences Key Laboratory of Polymer Physics and Chemistry and CAS Key Laboratories of Organic Solids Institute of Chemistry Chinese Academy of Sciences Beijing 100190 P. R. China

University of Chinese Academy of Sciences Beijing 100049 P. R. China

Beijing Advanced Innovation Center for Soft Matter Science and Engineering College of Life Science and Technology Beijing University of Chemical Technology Beijing 100029 P. R. China

Institute of Chinese Medical Sciences State Key Laboratory of Quality Research in Chinese Medicine University of Macau Macao 999078 P. R. China

Faculty of Chemistry and Biochemistry Ruhr‐University Bochum Universitätsstrasse 150 44780 Bochum Germany

Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School Central South University Changsha 410006 P. R. China

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China

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