Review
Immunology
Zhuoying Tian, Yue Zeng, Yurong Peng, Junqi Liu, Fang Wu
Summary: Activation of the cGAS-STING pathway by cytoplasmic DNA leads to the production of Type-1 interferons, which play a critical role in cancer-immunity cycle. Research has shown that combination therapy of STING agonists has made progress in preclinical and clinical trials, but selecting appropriate combination therapy regimens remains a challenge.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Oncology
Ziqi Liu, Dan Wang, Jiarong Zhang, Pingjuan Xiang, Zhaoyang Zeng, Wei Xiong, Lei Shi
Summary: The cGAS-STING signaling pathway plays a critical role in regulating the tumor microenvironment by affecting immune activation. It has been widely recognized for its ability to combat tumor progression and induce immune responses, leading to the development of immunotherapies. However, recent findings also suggest its diverse roles in shaping the tumor microenvironment, including functions that promote tumor progression.
Review
Chemistry, Inorganic & Nuclear
Jia Tan, Meifang Wang, Binbin Ding, Ping'an Ma, Jun Lin
Summary: The activation of STING in cancer cells promotes apoptosis and immune responses for immunotherapy. However, clinical application of STING agonists faces challenges. Nanotechnology provides new prospects for STING agonists, enabling tumor-specific delivery, improved efficiency, and reduced toxicity. This review discusses advanced nanoplatforms for STING agonists in immunotherapy, including different activation mechanisms and nanomaterials. Challenges and future directions are outlined for the translation of nano-sized STING agonists from bench to bedside.
COORDINATION CHEMISTRY REVIEWS
(2023)
Article
Chemistry, Multidisciplinary
M. Petrovic, G. Borchard, O. Jordan
Summary: Studies have shown the significance of the cGAS-STING pathway in anticancer immunity, but issues exist with cGAMP as a ligand, such as susceptibility to degradation and difficulty in transfecting into negatively charged membrane cells. Therefore, a suitable carrier is needed to enhance transfection efficiency and protect cGAMP.
JOURNAL OF CONTROLLED RELEASE
(2021)
Review
Immunology
Yu Gan, Xiaoying Li, Shuangze Han, Qi Liang, Xiaoqian Ma, Pengfei Rong, Wei Wang, Wei Li
Summary: The cGAS/STING pathway plays a crucial role in the immune system by recognizing abnormal DNA and activating the STING signaling pathway, leading to immune responses. However, chronic activation of STING may promote tumorigenesis in anticancer therapy.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Engineering, Biomedical
Qingbin He, Runxiao Zheng, Junchi Ma, Luyang Zhao, Yafang Shi, Jianfeng Qiu
Summary: In this study, a manganese-based nanoplatform was developed to responsively and efficiently activate cGAS-STING signaling pathway by generating more manganese ions and reactive oxygen species. Tumor responsiveness was achieved by exogenous and endogenous stimulation, which triggered the release of Mn2+ and enhanced ROS generation. This strategy provides a new approach to improve cancer immunotherapy.
BIOMATERIALS RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Jiarong Zhou, Christian J. Ventura, Ronnie H. Fang, Liangfang Zhang
Summary: Vaccines are widely explored for disease treatment and immunostimulatory adjuvants like STING signaling pathway have emerged as important therapeutic targets. Activating the STING pathway can generate potent immune responses. Nanocarriers can overcome challenges and broaden the application of STING vaccines.
MOLECULAR ASPECTS OF MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Hee Ra Jung, Seongman Jo, Min Jae Jeon, Hyelim Lee, Yeonjeong Chu, Jeehee Lee, Eunha Kim, Gyu Yong Song, Cheulhee Jung, Hyejin Kim, Sanghee Lee
Summary: In this study, a new chemical compound, KAS-08, was identified as an effective STING pathway activator in cancer immunotherapy. The activation of STING was achieved through direct binding or enhanced phosphorylation of STING and downstream effectors.
Article
Multidisciplinary Sciences
Xuan Wang, Yingqi Liu, Chencheng Xue, Yan Hu, Yuanyuan Zhao, Kaiyong Cai, Menghuan Li, Zhong Luo
Summary: This study introduces a nanoagonist based on BSA/ferritin that activates the cGAS-STING signaling pathway in DCs in solid tumor microenvironment, offering a promising approach for robust antitumor immunity.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Lingpu Zhang, Kun Shang, Xiaomin Li, Meifang Shen, Sheng Lu, Dongsheng Tang, Hongbin Han, Yingjie Yu
Summary: A reduction-sensitive polymer is designed to encapsulate a cationic phenanthriplatin drug into nanoparticles, which can release the drug in cancer cells and induce DNA damage and activate immune responses, improving the efficacy of chemo-immunotherapy.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Review
Immunology
Liang Ou, Ao Zhang, Yuxing Cheng, Ying Chen
Summary: The cGAS-STING signal pathway is an important innate immune signal pathway that plays a role in regulating cancer, autoimmune and inflammatory diseases, microbial and parasitic infectious diseases, as well as bridging innate immunity and adaptive immunity.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Kun Li, Yihang Gong, Dongbo Qiu, Hui Tang, Jian Zhang, Zenan Yuan, Yingqi Huang, Yunfei Qin, Linsen Ye, Yang Yang
Summary: The study found that the chemotherapy agent teniposide effectively activates the cGAS-STING signaling in HCC patients. Combining hyperbaric oxygen therapy can enhance the therapeutic effect of teniposide on HCC and improve the response to PD-1 immunotherapy.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Review
Engineering, Biomedical
Yongjuan Li, Xinyan Li, Jinmeng Yi, Yongjian Cao, Zhihai Qin, Zhiyuan Zhong, Weijing Yang
Summary: As the first line of host defense against pathogenic infections, innate immunity plays a key role in anti-tumor immunotherapy. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) (cGAS-STING) pathway and its activation of proinflammatory cytokines and chemokines have attracted attention for cancer immunotherapy. However, the limitations of small molecule STING agonists, such as fast excretion, low bioavailability, nonspecificity, and adverse effects, hinder their therapeutic efficacy. Nanodelivery systems with appropriate characteristics can address these challenges.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Multidisciplinary Sciences
You-Tong Wu, Yan Fang, Qi Wei, Heping Shi, Huiling Tan, Yafang Deng, Zhiqun Zeng, Jian Qiu, Chuo Chen, Lijun Sun, Zhijian J. Chen
Summary: The study demonstrates the development of antibody-drug conjugates (ADCs) by conjugating a STING agonist to tumor-targeting antibodies, which showed well-tolerated systemic administration and potent antitumor efficacy. The STING ADC also promoted multiple aspects of antitumor immune responses, highlighting its potential for clinical development.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Engineering, Biomedical
Lei Cao, Huixiang Tian, Man Fang, Zhe Xu, Dongsheng Tang, Juan Chen, Jiye Yin, Haihua Xiao, Kun Shang, Hongbin Han, Xiangping Li
Summary: This study developed a new nano delivery system to activate the cGAS-STING pathway and enhance the effect of chemotherapy and immunotherapy by releasing chemotherapeutic drugs cisplatin and camptothecin. It provides a new strategy for clinical antitumor therapy.
Article
Pharmacology & Pharmacy
Dandan Sun, Yifang Zou, Liu Song, Shulan Han, Hao Yang, Di Chu, Yun Dai, Jie Ma, Caitriona M. O'Driscoll, Zhuo Yu, Jianfeng Guo
Summary: This study confirms the potential of ginsenoside Rg3 as an inducer of immunogenic cell death (ICD) against colorectal cancer (CRC) cells. The effectiveness of Rg3 in inducing ICD is significantly enhanced when combined with quercetin (QTN) that induces reactive oxygen species (ROS). A targeted nanoparticle formulation, co-encapsulating Rg3 and QTN, is developed to improve the in vivo delivery and shows enhanced tumor targeting and prolonged blood circulation in a CRC mouse model. The combination of this nanoparticle formulation with anti-PD-L1 leads to significantly longer survival in animals.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Biotechnology & Applied Microbiology
Zhuo Yu, Jianfeng Guo, Yun Liu, Menglin Wang, Zhengsheng Liu, Yueqiu Gao, Leaf Huang
Summary: This study found that the characteristics of liver sinusoidal endothelial cells (LSECs) are closely related to the development and prognosis of fibrotic HCC. Simvastatin restores the quiescence of activated hepatic stellate cells (aHSCs) by stimulating LSECs and upregulating the expression of CXCL16 in LSECs. LSEC-targeted delivery of simvastatin not only alleviates LSEC capillarization, but also inhibits tumor progression by recruiting natural killer T (NKT) cells through CXCL16. Conclusion: Simvastatin has an immune-based therapeutic effect on remodeling the immunosuppressive tumor microenvironment in HCC, providing a new strategy for HCC treatment.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Article
Pharmacology & Pharmacy
Liu Song, Hao Yang, Di Liang, Di Chu, Leilei Yang, Meng Li, Bo Yang, Ying Shi, Zheng Chen, Zhuo Yu, Jianfeng Guo
Summary: Chlorogenic acid shows potential in promoting diabetic wound healing by reducing inflammation, enhancing re-epithelialization and angiogenesis, and facilitating collagen remodeling.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2022)
Article
Biochemical Research Methods
Jianfeng Guo, Leaf Huang
Summary: FOLFOX is an effective treatment for colorectal cancer and hepatocellular carcinoma, but its high toxicity limits the dosage. Two lipid-based nanoformulations, Nano-Folox and Nano-FdUMP, have been developed to lower toxicity and improve antitumor effect. The protocols for preparing these nanoformulations are described.
Article
Oncology
Zhuo Yu, Yuyao Li, Yue Li, Jinghao Zhang, Man Li, Longshan Ji, Yifei Tang, Yanxi Zheng, Jianguo Sheng, Qiucheng Han, Fu Li, Jianfeng Guo, Lingtai Wang, Xuehua Sun, Yueqiu Gao, Hai Feng
Summary: This study found that bufalin can promote the polarization of tumor-infiltrating macrophages (TIMs) towards the tumor-inhibitory M1 phenotype to improve the efficacy of immunotherapy for hepatocellular carcinoma (HCC). Bufalin inhibits the overexpression of p50 nuclear factor kappa B (NF-kappa B) factor and activates the NF-kappa B signaling pathway, resulting in the production of immunostimulatory cytokines and the activation of antitumor T cell immune response. Bufalin also enhances the antitumor activity of anti-PD-1 antibody in HCC.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Chemistry, Multidisciplinary
Shulan Han, Shengnan Bi, Tingting Guo, Dandan Sun, Yifang Zou, Lingzhi Wang, Liu Song, Di Chu, Anqi Liao, Xiaohuan Song, Zhuo Yu, Jianfeng Guo
Summary: This study confirmed the role of Plumbagin and Dihydrotanshinone I as inducers of immunogenic cell death in hepatocellular carcinoma (HCC) cells. The researchers developed a polymeric nanoparticle formulation that enhanced the delivery and tumor targeting of these drugs, leading to chemo-immunotherapeutic effects and significantly prolonged survival in HCC mice. This study provides a promising strategy for remodeling the immunosuppressive tumor microenvironment in liver cancer.
JOURNAL OF CONTROLLED RELEASE
(2022)
Review
Chemistry, Physical
Jianfeng Guo, Yifang Zou, Leaf Huang
Summary: Immunogenic cell death (ICD) activates the immune system to eliminate tumors. However, using chemotherapeutic drugs as ICD inducers in tumor immunotherapy faces challenges such as poor solubility, short circulation, non-specific distribution, and toxicity. Recent advances in nanotechnology and pharmaceutical formulation offer solutions to overcome these challenges.
Article
Pharmacology & Pharmacy
Yao Sun, Michael F. Cronin, Monique C. P. Mendonca, Jianfeng Guo, Caitriona M. O'Driscoll
Summary: Prostate cancer is a serious disease that poses a threat to men's health, and traditional treatments face challenges such as poor prognosis and tumor resistance. A sialic acid-targeted nanoparticle is developed to deliver specific siRNA to tumor-associated macrophages, inhibiting the growth and metastasis of prostate cancer cells.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Di Chu, Junjun Chen, Xingmei Liu, Anqi Liao, Xiaohuan Song, Yutong Li, Leilei Yang, Zheng Chen, Zhuo Yu, Jianfeng Guo
Summary: The failure of wound healing in diabetic patients can lead to lower limb disability and amputation. Current strategies for diabetic wound management are not effective, and new alternatives are urgently needed. This study demonstrated for the first time the pro-healing effects of the natural alkaloid tetramethylpyrazine (TMP) from Ligusticum chuanxiong Hort on diabetic wounds. TMP facilitated cutaneous healing by promoting macrophage polarization and accelerated wound closure when delivered topically with hyaluronic acid hydrogel. The findings highlight the potential of TMP-HA for clinical application in diabetic wound healing.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Pharmacology & Pharmacy
Ya-Nan Li, Xiaoju Shi, Dandan Sun, Shulan Han, Yifang Zou, Lingzhi Wang, Leilei Yang, Yutong Li, Ying Shi, Jianfeng Guo, Caitriona M. O'Driscoll
Summary: In this study, the potential of melarsoprol (MEL) for hepatocellular carcinoma (HCC) therapy was investigated for the first time using in vitro and in vivo experimental approaches. A folate-targeted polyethylene glycol-modified amphiphilic cyclodextrin nanoparticle was developed for safe, efficient and specific delivery of MEL. The targeted nanoformulation achieved cell-specific uptake, cytotoxicity, apoptosis and migration inhibition in HCC cells, and significantly prolonged the survival of mice with orthotopic tumor without causing toxicity.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Linlin Li, Yifang Zou, Lingzhi Wang, Leilei Yang, Yutong Li, Anqi Liao, Zheng Chen, Zhuo Yu, Jianfeng Guo, Shulan Han
Summary: This study confirmed the potential of scutellarin for inducing immunogenic cell death in hepatocellular carcinoma cells. To enable its in vivo application, a targeted nanocarrier was developed. The nanocarrier effectively delivered scutellarin to the tumor site and reversed the immune suppressive tumor microenvironment, resulting in improved therapeutic efficacy and increased survival in a mouse model of hepatocellular carcinoma, without causing toxicity.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Biotechnology & Applied Microbiology
Menglin Wang, Benoit Rousseau, Kunyu Qiu, Guannan Huang, Yu Zhang, Hang Su, Christine Le Bihan-Benjamin, Ines Khati, Oliver Artz, Michael B. Foote, Yung-Yi Cheng, Kuo-Hsiung Lee, Michael Z. Miao, Yue Sun, Philippe-Jean Bousquet, Marc Hilmi, Elise Dumas, Anne-Sophie Hamy, Fabien Reyal, Lin Lin, Paul M. Armistead, Wantong Song, Ava Vargason, Janelle C. Arthur, Yun Liu, Jianfeng Guo, Xuefei Zhou, Juliane Nguyen, Yongqun He, Jenny P. -Y. Ting, Aaron C. Anselmo, Leaf Huang
Summary: Research has shown that the tumor microbiota can influence cancer progression. Targeting anaerobic bacteria with pre-resection antibiotics significantly improves disease-free survival in colorectal cancer patients. By designing an antibiotic encapsulated in liposomes, tumor-associated bacteria can be eliminated without disrupting the gut microbiome, leading to enhanced anti-tumoral immunity and potential interventions in microbiome-immunotherapy.
NATURE BIOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Shulan Han, Xueying Bao, Yifang Zou, Lingzhi Wang, Yutong Li, Leilei Yang, Anqi Liao, Xuemei Zhang, Xin Jiang, Di Liang, Yun Dai, Qing-Chuan Zheng, Zhuo Yu, Jianfeng Guo
Summary: DL induces the transformation of M2 TAMs to M1 by modulating the PI3K/Akt signaling pathway, thereby remodeling the immunosuppressive tumor microenvironment in hepatocellular carcinoma (HCC) mice and enhancing the efficacy of anti-CD47 antibody for long-term animal survival.
