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Regulating metalloimmunology with nanomedicine for cancer therapy

Nano Research 2023年第12期16卷 13164-13181页

作者： Saibo Ma Lin Chen Muhammad Hamza Jing Chang Motao Zhu College of Marine Life Science Ocean University of ChinaQingdao 266003China CAS Key Laboratory for Biomedical Effects of Nanomaterials&Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijing 100190China Laboratory for Marine Drugs and Bioproducts Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266235China University of Chinese Academy of Sciences Beijing 100049China

Metals are essential components of both micronutrients and macronutrients in living organisms and are involved in a variety of immune processes in the forms of free ions or protein-coupled complexes(metalloproteins).Multiple aspects of the immune system,from the structural and functional control of immune-related proteins to the cellular responses to immunotherapy,could be affected by ***,the employment of metal for the regulation of immunity,termed as metalloimmunology,is gaining interest as a prevalent and efficacious approach to combating ***,the manipulation of metalloimmunology using traditional drugs presents several challenges,including limited bioavailability,adverse effects,and a lack of targeting *** review provides an overview of the latest findings in metal and metal-regulatory therapeutic agents for the treatment of *** trace metal elements,such as iron,zinc,copper,manganese,magnesium,and calcium,as well as heavy metal drugs and their mechanisms of action,will be discussed with a particular focus on their roles in regulating the tumor-immune *** latest nanotechnology employed in the administration of metal-regulatory drugs and the design concepts for tailored therapeutic interventions will be *** concepts and information offer promising clinical possibilities of modulating cancer immunology by targeting metal metabolism.

关键词： metalloimmunology metal metabolism cancer immunotherapy nano-enabled delivery system cGAS-STING pathway ferroptosis and cuprotosis

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Combining cisplatin and a STING agonist into one molecule for metalloimmunotherapy of cancer

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National Science Review 2024年第1期11卷 107-119页

作者： Shuren Zhang Dongfan Song Wenhao Yu Ji Li Xiaoyu Wang Yachao Li Zihan Zhao Qi Xue Jing Zhao Jie P.Li Zijian Guo State Key Laboratory of Coordination Chemistry School of Chemistry and Chemical EngineeringChemistry and Biomedicine Innovation Center (ChemBIC) Nanjing University Department of Urology Afflliated Drum Tower HospitalMedical SchoolNanjing University Nanchuang (Jiangsu)Institute of Chemistry and Health

Mounting evidence suggests that strategies combining DNA-damaging agents and stimulator of interferon genes(STING) agonists are promising cancer therapeutic regimens because they can amplify STING activation and remodel the immunosuppressive tumor microenvironment. However, a single molecular entity comprising both agents has not yet been developed. Herein, we designed two PtIV-MSA-2 conjugates(Ⅰand Ⅱ) containing the DNA-damaging chemotherapeutic drug cisplatin and the innate immuneactivating STING agonist MSA-2; these conjugates showed great potential as multispecific small-molecule drugs against pancreatic cancer. Mechanistic studies revealed that conjugate Ⅰ upregulated the expression of transcripts associated with innate immunity and metabolism in cancer cells, significantly differing from cisplatin and MSA-2. An analysis of the tumor microenvironment demonstrated that conjugate I could enhance the infiltration of natural killer(NK) cells into tumors and promote the activation of T cells, NK cells and dendritic cells in tumor tissues. These findings indicated that conjugate I, which was created by incorporating a Pt chemotherapeutic drug and STING agonist into one molecule, is a promising and potent anticancer drug candidate, opening new avenues for small-molecule-based cancer metalloimmunotherapy.

关键词： platinum drug STING agonist single-molecule multitarget metalloimmunology

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Converting bacteria into autologous tumor vaccine via surface biomineralization of calcium carbonate for enhanced immunotherapy

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Acta Pharmaceutica Sinica B 2023年第12期13卷 5074-5090页

作者： Lina Guo Jinsong Ding Wenhu Zhou Xiangya School of Pharmaceutical Sciences Central South UniversityChangsha 410013China Key Laboratory of Biological Nanotechnology of National Health Commission Xiangya HospitalChangsha 410008China

Autologous cancer vaccine that stimulates tumor-specific immune responses for personalized immunotherapy holds great potential for tumor ***,its efficacy is still suboptimal due to the immunosuppressive tumor microenvironment(ITM).Here,we report a new type of bacteria-based autologous cancer vaccine by employing calcium carbonate(CaCO_(3))biomineralized Salmonella(Sal)as an in-situ cancer vaccine producer and systematical ITM ***_(3) can be facilely coated on the Sal surface with calcium ionophore A23187 co-loading,and such biomineralization did not affect the bioactivities of the *** intratumoral accumulation,the CaCO_(3) shell was decomposed at an acidic microenvironment to atenuate tumor acidity,accompanied by the release of Sal and Ca^(2+)/***,Sal served as a cancer vaccine producer by inducing cancer cells'immunogenic cell death(ICD)and promoting the gap junction formation between tumor cells and dendritic cells(DCs)to promote antigen ***^(2+),on the other hand,was intermalized into various types of immune cells with the aid of A23187 and synergized with Sal to systematically regulate the immune system,including DCs maturation,macrophages polarization,and T cells *** a result,such bio-vaccine achieved remarkable effcacy against both primary and metastatic tumors by eliciting potent anti-tumor immunity with full *** work demonstrated the potential of bioengineered bacteria as bio-active vaccines for enhanced tumor immunotherapy.

关键词： Bacteria-mediated cancer therapy Tumor microenvironment Calcium carbonate Mineralization metalloimmunology Autologous tumor vaccine Immunotherapy Tumor metastasis

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