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Cancer Nanobombs Delivering Artoxplatin with a Polyigniter Bearing Hydrophobic Ferrocene Units Upregulate PD-L1 Expression and Stimulate Stronger Anticancer Immunity
Gao,Yongchao1,2,3,4; Zhang,Hanchen5,6; Tang,Lin7; Li,Feifei7; Yang,Li8; Xiao,Haihua5,6; Karges,Johannes9; Huang,Weihua1,2,3,4; Zhang,Wei1,2,3,4,10,11; Liu,Chaoyong7
2024-01-26
Source PublicationAdvanced Science
ISSN2198-3844
Volume11Issue:4Pages:2300806
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.

KeywordArtoxplatin Chemo-immunotherapy Immunogenic Cell Death Oxaliplatin Reactive Oxygen Species
DOI10.1002/advs.202300806
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaChemistry ; Science & Technology - Other Topics ; Materials Science
WOS SubjectChemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary
WOS IDWOS:000985887000001
PublisherWILEY, 111 RIVER ST, HOBOKEN 07030-5774, NJ
Scopus ID2-s2.0-85159084562
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Citation statistics
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
THE STATE KEY LABORATORY OF QUALITY RESEARCH IN CHINESE MEDICINE (UNIVERSITY OF MACAU)
Corresponding AuthorZhang,Wei; Liu,Chaoyong
Affiliation1.Department of Clinical Pharmacology,Xiangya Hospital,Central South University,Changsha,87 Xiangya Road,410008,China
2.Institute of Clinical Pharmacology,Central South University,Hunan Key Laboratory of Pharmacogenetics,Changsha,110 Xiangya Road,410078,China
3.Engineering Research Center of Applied Technology of Pharmacogenomics,Ministry of Education,Changsha,110 Xiangya Road,410078,China
4.National Clinical Research Center for Geriatric Disorders,Changsha,87 Xiangya Road, Hunan,410008,China
5.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,China
6.University of Chinese Academy of Sciences,Beijing,100049,China
7.Beijing Advanced Innovation Center for Soft Matter Science and Engineering,College of Life Science and Technology,Beijing University of Chemical Technology,Beijing,100029,China
8.Institute of Chinese Medical Sciences,State Key Laboratory of Quality Research in Chinese Medicine,University of Macau,999078,Macao
9.Faculty of Chemistry and Biochemistry,Ruhr-University Bochum,Bochum,Universitätsstrasse 150,44780,Germany
10.Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya Medical School,Central South University,Changsha,410006,China
11.Key Specialty of Clinical Pharmacy,The First Affiliated Hospital of Guangdong Pharmaceutical University,Guangzhou,510080,China
Recommended Citation
GB/T 7714
Gao,Yongchao,Zhang,Hanchen,Tang,Lin,et al. Cancer Nanobombs Delivering Artoxplatin with a Polyigniter Bearing Hydrophobic Ferrocene Units Upregulate PD-L1 Expression and Stimulate Stronger Anticancer Immunity[J]. Advanced Science, 2024, 11(4), 2300806.
APA Gao,Yongchao., Zhang,Hanchen., Tang,Lin., Li,Feifei., Yang,Li., Xiao,Haihua., Karges,Johannes., Huang,Weihua., Zhang,Wei., & Liu,Chaoyong (2024). Cancer Nanobombs Delivering Artoxplatin with a Polyigniter Bearing Hydrophobic Ferrocene Units Upregulate PD-L1 Expression and Stimulate Stronger Anticancer Immunity. Advanced Science, 11(4), 2300806.
MLA Gao,Yongchao,et al."Cancer Nanobombs Delivering Artoxplatin with a Polyigniter Bearing Hydrophobic Ferrocene Units Upregulate PD-L1 Expression and Stimulate Stronger Anticancer Immunity".Advanced Science 11.4(2024):2300806.
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