Synthetic High‐Density Lipoprotein Mimicking Nanodiscs with Pt(IV) Prodrug Enable Tumor Targeting and cGAS‐STING Pathway Activation for Chemo‐Immunotherapy
Abstract
Abstract Cisplatin is a first‐line, broad‐spectrum anti‐tumor drug used to treat various types of cancer. However, immune‐suppressive tumor microenvironments (TME) are often induced by cisplatin. Here, a first synthetic high‐density lipoprotein (sHDL) nanodisc, referred as sHDL@Pt, is engineered to load a Pt(IV) prodrug (C2‐Pt(IV)‐C12), inducing a 2.2‐fold increase in dsDNA release compared to cisplatin. This further activates the innate immune system through the cGAS‐STING pathway. Using near‐infrared II fluorescence imaging and single photon emission computed tomography imaging technology, it is found that sHDL@Pt can be effectively accumulated in tumor sites. The sHDL@Pt can induce severe DNA damage, which subsequently results in a more pronounced activation of the cGAS‐STING pathway, further promoting dendritic cell maturation and T cell proliferation, triggering strong cytotoxic T lymphocyte responses, and inhibiting tumor growth. This work introduces a novel approach for delivering Pt(IV) prodrug that effectively initiates and activates innate immunity through the activation of the cGAS‐STING pathway.
Article Details
Authors (12)
Kun Shang
Dongsheng Tang
Synergetic Innovation Center for Quantum Effects and Application, Key Laboratory of Low-dimensional Quantum Structures and Quantum Control of Ministry of Education, Key Laboratory for Multifunctional Ionic Electronic Materials and Devices, College of Physics and Electronics, Hunan Normal University , Changsha 410081, Hunan,
Minhui Cui
Beijing National Laboratory for Molecular Sciences Laboratory of Polymer Physics and Chemistry Institute of Chemistry Chinese Academy of Sciences Beijing 100190 P. R. China
Hongyi Hou
Department of Obstetrics and Gynecology Peking University People's Hospital Beijing 100044 P. R. China
Bing Xiao
Department of Orthopaedics
Jinjian Liu
State Key Laboratory of Advanced Medical Materials and Devices Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine Key Laboratory of Radiopharmacokinetics for Innovative Drugs Tianjin Institutes of Health Science Institute of Radiation Medicine Chinese Academy of Medical Sciences & Peking Union Medical College Tianjin 300192 P. R. China
Ruoshi Zhang
School of Pharmaceutical Sciences Tsinghua University Beijing 100084 P. R. China
Rui Kuai
Jianfeng Liu
Haihua Xiao
Beijing National Laboratory for Molecular Sciences Laboratory of Polymer Physics and Chemistry Institute of Chemistry Chinese Academy of Sciences Beijing P. R. China
Fan Huang
State Key Laboratory of Advanced Medical Materials and Devices, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Key Laboratory of Radiopharmacokinetics for Innovative Drugs, Tianjin Institutes of Health Science, Institute of Radiation Medicine
Jianliu Wang