Xing Duan

Sichuan University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Xiangrong Song

Sichuan University

Shugang Qin

University of Electronic Science and Technology of China

Hai Huang

Xiamen University of Technology

Mengran Guo

Beijing University of Chinese Medicine

Wen Xiao

Affiliated Hospital of Shandong University of Traditional Chinese Medicine

Na Fan

Inner Mongolia University

Yupei Zhang

Sichuan University

Kepan Chen

Fudan University

Xi He

Sichuan University

Qian Zheng

Guiyang Medical University

Cooperative Institutions

Sichuan University

West China Hospital of Sichuan University

State Key Laboratory of Biotherapy

Macau University of Science and Technology

Shihezi University

Tianjin Institute of Pharmaceutical Research (China)

Chinese Academy of Medical Sciences & Peking Union Medical College

West China Medical Center of Sichuan University

Chinese Academy of Sciences

Chengdu University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Dual-targeting tigecycline nanoparticles for treating intracranial infections caused by multidrug-resistant Acinetobacter baumannii

Journal of Nanobiotechnology (2024)

Lan Xing Shugang Qin Huan Liu Mengran Guo Yupei Zhang

Abstract Multidrug-resistant (MDR) Acinetobacter baumannii ( A. baumannii ) is a formidable pathogen responsible for severe intracranial infections post-craniotomy, exhibiting a mortality rate as high as 71%. Tigecycline (TGC), a broad-spectrum antibiotic, emerged as a potential therapeutic agent for MDR A. baumannii infections. Nonetheless, its clinical application was hindered by a short in vivo half-life and limited permeability through the blood–brain barrier (BBB). In this study, we prepared a novel core–shell nanoparticle encapsulating water-soluble tigecycline using a blend of mPEG-PLGA and PLGA materials. This nanoparticle, modified with a dual-targeting peptide Aβ11 and Tween 80 (Aβ11/T80@CSs), was specifically designed to enhance the delivery of tigecycline to the brain for treating A. baumannii -induced intracranial infections. Our findings demonstrated that Aβ11/T80@CSs nanocarriers successfully traversed the BBB and effectively delivered TGC into the cerebrospinal fluid (CSF), leading to a significant therapeutic response in a model of MDR A. baumannii intracranial infection. This study offers initial evidence and a platform for the application of brain-targeted nanocarrier delivery systems, showcasing their potential in administering water-soluble anti-infection drugs for intracranial infection treatments, and suggesting promising avenues for clinical translation. Graphical abstract

Tigecycline

Acinetobacter baumannii

Nanocarriers

10.1186/s12951-024-02373-z

Cite

Citations (2)

mRNA Vaccines Against SARS‐CoV‐2 Variants Delivered by Lipid Nanoparticles Based on Novel Ionizable Lipids

Advanced Functional Materials (2022)

Kepan Chen Na Fan Hai Huang Xin Jiang Shugang Qin

Abstract SARS‐CoV‐2 variants are now still challenging all the approved vaccines, including mRNA vaccines. There is an urgent need to develop new generation mRNA vaccines with more powerful efficacy and better safety against SARS‐CoV‐2 variants. In this study, a new set of ionizable lipids named 4N4T are constructed and applied to form novel lipid nanoparticles called 4N4T‐LNPs. Leading 4N4T‐LNPs exhibit much higher mRNA translation efficiency than the approved SM‐102‐LNPs. To test the effectiveness of the novel delivery system, the DS mRNA encoding the full‐length S protein of the SARS‐CoV‐2 variant is synthesized and loaded in 4N4T‐LNPs. The obtained 4N4T‐DS mRNA vaccines successfully trigger robust and durable humoral immune responses against SARS‐CoV‐2 and its variants including Delta and Omicron. Importantly, the novel vaccines have higher RBD‐specific IgG titers and neutralizing antibody titers than SM‐102‐based DS mRNA vaccine. Besides, for the first time, the types of mRNA vaccine‐induced neutralizing antibodies are found to be influenced by the chemical structure of ionizable lipids. 4N4T‐DS mRNA vaccines also induce strong Th1‐skewed T cell responses and have good safety. This work provides a novel vehicle for mRNA delivery that is more effective than the approved LNPs and shows its application in vaccines against SARS‐CoV‐2 variants.

Vaccine efficacy

10.1002/adfm.202204692

Cite

Citations (65)

mRNA-LNP vaccination-based immunotherapy augments CD8+ T cell responses against HPV-positive oropharyngeal cancer

npj Vaccines (2023)

Ke Qiu Xing Duan Minzi Mao Yao Song Yufang Rao

Abstract Although mRNA vaccines are known as potent activators of antigen-specific immune responses against infectious diseases, limited understanding of how they drive the functional commitment of CD8 + T cells in tumor microenvironment (TME) and secondary lymphoid organs hinders their broader application in cancer immunotherapy. Here, we systematically evaluated the immunological effects of a lipid nanoparticle (LNP)-encapsulated mRNA vaccine that encodes human papillomavirus E7 protein (HPV mRNA-LNP), a tumor-specific antigen of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). HPV mRNA-LNP vaccination activated overall and HPV-specific CD8 + T cells, as well as differentially drove the functional commitment of CD8 + T cells through distinct IFN-response and exhaustion trajectories in the spleen and TME, respectively. Combination therapies of HPV mRNA-LNP vaccination with immune checkpoint blockades boosted HPV-specific CD8 + T cells while maintaining their anti-tumor function, thus further promoting tumor regression. Our results showed that the HPV mRNA-LNP vaccination combined with immune checkpoint blockade is a promising approach for immunotherapy of HPV-positive OPSCC.

Cancer Immunotherapy

Immune checkpoint

10.1038/s41541-023-00733-8

Cite

Citations (21)

Lipid Nanoparticle Delivery System for mRNA Encoding B7H3‐redirected Bispecific Antibody Displays Potent Antitumor Effects on Malignant Tumors

Advanced Science (2022)

Cheng Huang Xing Duan Jichao Wang Qingqing Tian Yangmei Ren

The therapeutic use of bispecific T-cell engaging (BiTE) antibodies has shown great potential for treating malignancies. BiTE can simultaneously engage CD3ε on T cells and tumor antigen on cancer cells, thus exerting an effective antitumor effect. Nevertheless, challenges in production, manufacturing, and short serum half-life of BiTE have dampened some of the promise and impeded the pace of BiTE-based therapeutics to combat diseases. Nowadays, in vitro-transcribed mRNA has achieved programmed production, which is more flexible and cost-effective than the traditional method of producing recombinant antibody. Here, the authors have developed a BiTE-based mRNA treatment by encapsulating mRNA encoding B7H3×CD3 BiTE into a novel ionizable lipid nanoparticles (LNPs). The authors have found that LNPs have high transfection efficiency, and the hepatosplenic targeting capability of produce high concentrations of BiTE. Above all, a single intravenous injection of BiTE mRNA-LNPs could achieve high levels of protein expression in vivo and significantly prolonged the half-life of the BiTE, which can elicit robust and durable antitumor efficacy against hematologic malignancies and melanoma. Therefore, their results suggested that the therapeutic strategy based on mRNA expression of B7H3×CD3 BiTE is of potential research value and has promising clinical application prospects.

Bispecific antibody

Delivery system

10.1002/advs.202205532

Cite

Citations (33)

Dual-targeting tigecycline nanoparticles for treating intracranial infections caused by multidrug-resistant Acinetobacter baumannii

Research Square (Research Square) (2024)

Lan Xing Shugang Qin Huan Liu Mengran Guo Yupei Zhang

Abstract Multidrug-resistant (MDR) Acinetobacter baumannii ( A. baumannii ) is a formidable pathogen responsible for severe intracranial infections post-craniotomy, exhibiting a mortality rate as high as 71%. Tigecycline (TGC), a broad-spectrum antibiotic, emerged as a potential therapeutic agent for MDR A. baumannii infections. Nonetheless, its clinical application was hindered by a short in vivo half-life and limited permeability through the blood-brain barrier (BBB). In this study, we developed a novel nanocarrier, integrating a dual-targeting peptide Aβ11 and Tween 80 modification (Aβ11/T80@CSs), specifically designed to enhance TGC delivery to the brain for treating A. baumannii -induced intracranial infections. Our findings demonstrated that Aβ11/T80@CSs nanocarriers successfully traversed the BBB and effectively delivered TGC into the cerebrospinal fluid (CSF), leading to a significant therapeutic response in a model of MDR A. baumannii intracranial infection. This study offers initial evidence and a platform for the application of brain-targeted nanocarrier delivery systems, showcasing their potential in administering water-soluble anti-infection drugs for intracranial infection treatments, and suggesting promising avenues for clinical translation.

Tigecycline

Acinetobacter baumannii

Nanocarriers

10.21203/rs.3.rs-3807612/v1

Cite

Citations (0)

A novel heterologous receptor-binding domain dodecamer universal mRNA vaccine against SARS-CoV-2 variants

Acta Pharmaceutica Sinica B (2023)

Shugang Qin Hai Huang Wen Xiao Kepan Chen Xi He

There are currently approximately 4,000 mutations in the SARS-CoV-2 S protein gene and emerging SARS-CoV-2 variants continue to spread rapidly worldwide. Universal vaccines with high efficacy and safety urgently need to be developed to prevent SARS-CoV-2 variants pandemic. Here, we described a novel self-assembling universal mRNA vaccine containing a heterologous receptor-binding domain (HRBD)-based dodecamer (HRBD

Heterologous

HEK 293 cells

10.1016/j.apsb.2023.01.010

Cite

Citations (6)

Insights into the formulation of lipid nanoparticles for the optimization of mRNA therapeutics

Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology (2024)

Xiangyu Jiao Xi He Shugang Qin Xiaoling Yin Tingting Song

Abstract mRNA‐based therapeutics increasingly demonstrate significant potential in treating various diseases, including infectious diseases, cancers, and genetic disorders. Effective delivery systems are crucial for advancing mRNA therapeutics. Lipid nanoparticles (LNPs) serve as an excellent carrier, widely validated for their safety and tolerability in commercially available mRNA vaccines. Standard LNPs typically consist of four components: ionizable lipids (ILs), helper lipids, cholesterol, and polyethylene glycol‐lipids (PEG‐lipids), with the structural design of ILs gradually becoming a focal point of research interest. The chemical structures and formulations of the other components also significantly affect the delivery efficiency, targeting specificity, and stability of LNPs. The complex formulations of LNPs may hinder the clinical transformation of mRNA therapeutics and have raised widespread concerns about their safety. This review aims to summarize the progress of LNPs‐based mRNA therapeutics in clinical trials, focusing on adverse effects that occurred during these trials. It also discusses representative innovations in LNP components, highlighting challenges and potential ways in this research field. We firmly believe this review will promote further improvements and designs of LNP compositions to optimize mRNA therapeutics. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology‐Inspired Nanomaterials > Lipid‐Based Structures

Tolerability

10.1002/wnan.1992

Cite

Citations (2)

Sodium alginate coating simultaneously increases the biosafety and immunotherapeutic activity of the cationic mRNA nanovaccine

Acta Pharmaceutica Sinica B (2022)

Xing Duan Yi Zhang Mengran Guo Na Fan Kepan Chen

The extraordinary advantages associated with mRNA vaccines, including their high efficiency, relatively low severity of side effects, and ease of manufacture, have enabled them to be a promising immunotherapy approach against various infectious diseases and cancers. Nevertheless, most mRNA delivery carriers have many disadvantages, such as high toxicity, poor biocompatibility, and low efficiency in vivo, which have hindered the widespread use of mRNA vaccines. To further characterize and solve these problems and develop a new type of safe and efficient mRNA delivery carrier, a negatively charged SA@DOTAP-mRNA nanovaccine was prepared in this study by coating DOTAP-mRNA with the natural anionic polymer sodium alginate (SA). Intriguingly, the transfection efficiency of SA@DOTAP-mRNA was significantly higher than that of DOTAP-mRNA, which was not due to the increase in cellular uptake but was associated with changes in the endocytosis pathway and the strong lysosome escape ability of SA@DOTAP-mRNA. In addition, we found that SA significantly increased the expression of LUC-mRNA in mice and achieved certain spleen targeting. Finally, we confirmed that SA@DOTAP-mRNA had a stronger antigen-presenting ability in E. G7-OVA tumor-bearing mice, dramatically inducing the proliferation of OVA-specific CLTs and ameliorating the antitumor effect. Therefore, we firmly believe that the coating strategy applied to cationic liposome/mRNA complexes is of potential research value in the field of mRNA delivery and has promising clinical application prospects.

Cancer Immunotherapy

10.1016/j.apsb.2022.08.015

Cite

Citations (21)

Nanomedicine for Targeting Delivery of Gene and Other DNA / RNA Therapies Based Viruses Engineering

Nanomedicine (2024)

Xiangrong Song Mengran Guo Zhongshan He Xing Duan Wen Xiao

In recent years, gene therapy, a revolutionary medical technology, has changed the current treatment status of monogenic genetic diseases and led to new choices for tumors, genetic diseases, autoimmune diseases, etc. Targeting the delivery of gene-based nanomedicine to specific sites in the body is essential for efficient disease treatment. At present, various delivery platforms, such as viral vectors and nanoparticles, have been incorporated into the development and clinical use of gene-based drugs. By engineering different types of nanoparticles, the targeted accumulation of gene-based nanomedicine in specific organs can be achieved. In this section, we introduce strategies for the targeted delivery of gene-based nanomedicines to different tissues, such as tumors, liver, spleen, lymph nodes, lungs, and brain, and discuss the importance of the targeted delivery of gene-based nanomedicines for successful treatment outcomes.

10.1002/9783527830404.ch7

Cite

Citations (0)

Fundamentals in Nanomedicine

Nanomedicine (2024)

Xiangrong Song Mengran Guo Zhongshan He Xing Duan Wen Xiao

Since the first nanomedicine, amphotericin B liposomes (AmBisome®), were successfully approved for use in the market in 1990, nanomedicine has entered a period of rapid development. Compared with other dosage forms of drugs, nanomedicines have the unique advantages of improving the stability of drugs, prolonging the retention time in the circulation system, reducing drug-related adverse reactions and achieving targeted delivery. Moreover, nanomedicines show great potential for improving tissue distribution and bioavailability. In this section, we introduce the design theory of nanomedicines, progress in the controlled synthesis of nanomaterials, and progress in the surface modification and functionalization of nanomaterials for nanomedicines. We also discussed the application prospects of these methods in nanomedicines.

10.1002/9783527830404.ch2

Cite

Citations (0)