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6. Immune cell-mediated drug delivery for the treatment of inflammatory diseases

Author

Che, Junyi, Stevens, Molly, Sattler, Susanne, and Stingelin, Natalie

Abstract

Uncontrolled inflammation is a major pathological factor underlying a range of diseases including autoimmune conditions, cardiovascular disease and cancer. Improving localised delivery of immunosuppressive drugs to inflamed tissue in a non-invasive manner offers significant promise to reduce severe side effects caused by systemic administration. Employing immune cells for active transport of drugs and drug-loaded nanocarriers to a target site is a promising recent approach. Particularly, in the context of drug delivery for anti-inflammation therapy, immune cells have the intrinsic functions to migrate to and infiltrate the inflamed tissue. Here, a delivery strategy using neutrophils loaded with methotrexate (MTX)-liposomes ex vivo to deliver MTX to target sites was first investigated in vitro. This hybrid system efficiently migrated following an inflammatory chemokine gradient and triggered release of loaded liposomes via neutrophil extracellular traps (NETs) formation in an inflammatory environment was achieved. Subsequent re-uptake of the released liposomes by target macrophages provided detailed support for in vivo treatment studies. In parallel, macrophages were evaluated as alternative immune cells to carry nanoparticles. Given the advantage of a well-defined release mechanism (NETs formation), MTX-liposome loaded neutrophils were chosen over a macrophage-based system to be further validated in vivo using two mouse models of inflammation, a lipopolysaccharide (LPS)-injury skeletal muscle model and a myocardial ischemia reperfusion injury (IRI) model. The migratory behaviour of liposome-loaded neutrophils was confirmed by demonstrating the neutrophil-mediated delivery of liposomes to the inflamed muscle and the injured heart. A single low-dose injection of the hybrid system locally reduced inflammatory cytokine levels in the inflamed muscle and slightly improved the pumping efficiency of the IRI heart. These results highlight the advantages of immune cell-mediated drug delivery, which is a versatile strategy that allows combinations with different types of nanoparticles encapsulating various drugs to reduce tissue inflammation and actively promote repair in inflammatory diseases.

Published
2020
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10. Should Luxury Cosmetic Brands Turn to Focus on Influencer Marketing or Keep Their Traditional Marketing Strategy?

Author

He, Yijia, Pi, Mingyue, Che, Jiayue, Che, Junyi, Appolloni, Andrea, Series Editor, Caracciolo, Francesco, Series Editor, Ding, Zhuoqi, Series Editor, Gogas, Periklis, Series Editor, Huang, Gordon, Series Editor, Nartea, Gilbert, Series Editor, Ngo, Thanh, Series Editor, Striełkowski, Wadim, Series Editor, Jiang, Yushi, editor, Shvets, Yuriy, editor, and Mallick, Hrushikesh, editor

Published
2022
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19. Robotic Grasping and Manipulation Competition @IROS2016: Team Tsinghua

Author

Sun, Fuchun, Liu, Huaping, Fang, Bin, Guo, Di, Kong, Tao, Yang, Chao, Huang, Yao, Jing, Mingxuan, Che, Junyi, Barbosa, Simone Diniz Junqueira, Series Editor, Filipe, Joaquim, Series Editor, Kotenko, Igor, Series Editor, Sivalingam, Krishna M., Series Editor, Washio, Takashi, Series Editor, Yuan, Junsong, Series Editor, Zhou, Lizhu, Series Editor, Sun, Yu, editor, and Falco, Joe, editor

Published
2018
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21. Reactive Microneedle Patches with Antibacterial and Dead Bacteria‐Trapping Abilities for Skin Infection Treatment.

Author

Shan, Jingyang, Wu, Xiangyi, Che, Junyi, Gan, Jingjing, and Zhao, Yuanjin

Subjects
SKIN infections, BACTERIAL inactivation, BACTERIAL diseases, TREATMENT effectiveness, FIBROBLASTS
Abstract

Bacterial skin infections are highly prevalent and pose a significant public health threat. Current strategies are primarily focused on the inhibition of bacterial activation while disregarding the excessive inflammation induced by dead bacteria remaining in the body and the effect of the acidic microenvironment during therapy. In this study, a novel dual‐functional MgB2 microparticles integrated microneedle (MgB2 MN) patch is presented to kill bacteria and eliminate dead bacteria for skin infection management. The MgB2 microparticles not only can produce a local alkaline microenvironment to promote the proliferation and migration of fibroblasts and keratinocytes, but also achieve >5 log bacterial inactivation. Besides, the MgB2 microparticles effectively mitigate dead bacteria‐induced inflammation through interaction with lipopolysaccharide (LPS). With the incorporation of these MgB2 microparticles, the resultant MgB2 MN patches effectively kill bacteria and capture dead bacteria, thereby mitigating these bacteria‐induced inflammation. Therefore, the MgB2 MN patches show good therapeutic efficacy in managing animal bacterial skin infections, including abscesses and wounds. These results indicate that reactive metal borides‐integrated microneedle patches hold great promise for the treatment of clinical skin infections. [ABSTRACT FROM AUTHOR]

Published
2024
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24. Dexamethasone-Integrated Mesenchymal Stem Cells for Systemic Lupus Erythematosus Treatment viaMultiple Immunomodulatory Mechanisms

Author

Ma, Wenjuan, Che, Junyi, Chen, Weiwei, Wang, Dandan, Zhang, Huayong, and Zhao, Yuanjin

Abstract

The therapeutic application of mesenchymal stem cells (MSCs) has good potential as a treatment strategy for systemic lupus erythematosus (SLE), but traditional MSC therapy still has limitations in effectively modulating immune cells. Herein, we present a promising strategy based on dexamethasone liposome-integrated MSCs (Dexlip-MSCs) for treating SLE viamultiple immunomodulatory pathways. This therapeutic strategy prolonged the circulation time of dexamethasone liposomes in vivo, restrained CD4+T-cell proliferation, and inhibited the release of proinflammatory mediators (IFN-γ and TNF-α) by CD4+T cells. In addition, Dexlip-MSCs initiated cellular reprogramming by activating the glucocorticoid receptor (GR) signaling pathway to upregulate the expression of anti-inflammatory factors such as cysteine-rich secretory protein LCCL-containing domain 2 (CRISPLD2) and downregulate the expression of proinflammatory factors. In addition, Dexlip-MSCs synergistically increased the anti-inflammatory inhibitory effect of CD4+T cells through the release of dexamethasone liposomes or Dex-integrated MSC-derived exosomes (Dex-MSC-EXOs). Based on these synergistic biological effects, we demonstrated that Dexlip-MSCs alleviated disease progression in MRL/lpr mice more effectively than Dexlip or MSCs alone. These features indicate that our stem cell delivery strategy is a promising therapeutic approach for clinical SLE treatment.

Published
2024
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25. Glycyrrhetinic Acid Liposomes Encapsulated Microcapsules from Microfluidic Electrospray for Inflammatory Wound Healing.

Author

Zhi, Yue, Che, Junyi, Zhu, Haofang, Liu, Rui, and Zhao, Yuanjin

Subjects
*WOUND healing, *LIPOSOMES
Abstract

In diabetic wound healing, M1 macrophage accumulation and elevated inflammation are prevalent issues. Intelligent delivery systems that can sustainably release antioxidizing and anti‐inflammatory ingredients are expected for effective wound healing. Herein, a novel glycyrrhetinic acid (GA) liposomes encapsulated microcapsules delivery system that has desired features for inflammatory wound repair is presented. As the bacteria could break down the alginate shells, the GA liposomes could be controllably released from the microcapsules, which promotes M2 macrophage polarization and regulate their responses in the inflammatory wound microenvironment. Based on these, it is demonstrated that the GA liposomes encapsulated microcapsules delivery system exhibits an anti‐inflammatory and immunomodulatory effect for diabetic wound healing in a full‐thickness defect model in diabetic rats. These results indicate that the immunomodulatory capabilities of the microcapsules can be unitized for efficient wound repair, and such a delivery system is valuable for clinical wound healing applications. [ABSTRACT FROM AUTHOR]

Published
2023
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29. Block Length‐Dependent Protein Fouling on Poly(2‐oxazoline)‐Based Polymersomes: Influence on Macrophage Association and Circulation Behavior

Author

Najer, Adrian, primary, Belessiotis‐Richards, Alexis, additional, Kim, Hyemin, additional, Saunders, Catherine, additional, Fenaroli, Federico, additional, Adrianus, Christopher, additional, Che, Junyi, additional, Tonkin, Renée L., additional, Høgset, Håkon, additional, Lörcher, Samuel, additional, Penna, Matthew, additional, Higgins, Stuart G., additional, Meier, Wolfgang, additional, Yarovsky, Irene, additional, and Stevens, Molly M., additional

Published
2022
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31. Potent Virustatic Polymer–Lipid Nanomimics Block Viral Entry and Inhibit Malaria Parasites In Vivo

Author

Najer, Adrian, primary, Blight, Joshua, additional, Ducker, Catherine B., additional, Gasbarri, Matteo, additional, Brown, Jonathan C., additional, Che, Junyi, additional, Høgset, Håkon, additional, Saunders, Catherine, additional, Ojansivu, Miina, additional, Lu, Zixuan, additional, Lin, Yiyang, additional, Yeow, Jonathan, additional, Rifaie-Graham, Omar, additional, Potter, Michael, additional, Tonkin, Renée, additional, Penders, Jelle, additional, Doutch, James J., additional, Georgiadou, Athina, additional, Barriga, Hanna M. G., additional, Holme, Margaret N., additional, Cunnington, Aubrey J., additional, Bugeon, Laurence, additional, Dallman, Margaret J., additional, Barclay, Wendy S., additional, Stellacci, Francesco, additional, Baum, Jake, additional, and Stevens, Molly M., additional

Published
2022
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36. Controlled Dendrimersome Nanoreactor System for Localized Hypochlorite-Induced Killing of Bacteria

Author

Potter, Michael, primary, Najer, Adrian, additional, Klöckner, Anna, additional, Zhang, Shaodong, additional, Holme, Margaret N., additional, Nele, Valeria, additional, Che, Junyi, additional, Massi, Lucia, additional, Penders, Jelle, additional, Saunders, Catherine, additional, Doutch, James J., additional, Edwards, Andrew M., additional, Ces, Oscar, additional, and Stevens, Molly M., additional

Published
2020
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37. Neutrophils Enable Local and Non‐Invasive Liposome Delivery to Inflamed Skeletal Muscle and Ischemic Heart

Author

Che, Junyi, primary, Najer, Adrian, additional, Blakney, Anna K., additional, McKay, Paul F., additional, Bellahcene, Mohamed, additional, Winter, Charles W., additional, Sintou, Amalia, additional, Tang, Jiaqing, additional, Keane, Timothy J., additional, Schneider, Michael D., additional, Shattock, Robin J., additional, Sattler, Susanne, additional, and Stevens, Molly M., additional

Published
2020
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42. Biodegradable and biocompatible cationic polymer delivering microRNA-221/222 promotes nerve regeneration after sciatic nerve crush

Author

Song,Jialin, Li,Xueyang, Li,Yingli, Che,Junyi, Li,Xiaoming, Zhao,Xiaotian, Chen,Yinghui, Zheng,Xianyou, Yuan,Weien, Song,Jialin, Li,Xueyang, Li,Yingli, Che,Junyi, Li,Xiaoming, Zhao,Xiaotian, Chen,Yinghui, Zheng,Xianyou, and Yuan,Weien

Abstract

Jialin Song,1,2 Xueyang Li,3 Yingli Li,4,5 Junyi Che,6 Xiaoming Li,6 Xiaotian Zhao,6 Yinghui Chen,7,* Xianyou Zheng,1,* Weien Yuan6,* 1Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 2Department of Orthopedics, Shanghai University of Medicine and Health, Shanghai, Sixth People’s Hospital East Campus, Shanghai, 3Department of Plastic and Reconstructive Surgery, Xuzhou Medical College Affiliated Hospital, Xuzhou, Jiangsu, 4Department of Plastic Surgery, The General Hospital of Jinan Military Command, Jinan, Shandong, 5Department of Plastic Surgery, Chang Hai Hospital, Second Military Medical University, 6School of Pharmacy, Shanghai Jiao Tong University, 7Department of Neurology, Jinshan Hospital, Fudan University, JinShan District, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: MicroRNA (miRNA) has great potential to treat a wide range of illnesses by regulating the expression of eukaryotic genes. Biomaterials with high transfection efficiency and low toxicity are needed to deliver miRNA to target cells. In this study, a biodegradable and biocompatible cationic polymer (PDAPEI) was synthetized from low molecular weight polyethyleneimine (PEI1.8kDa) cross-linked with 2,6-pyridinedicarboxaldehyde. PDAPEI showed a lower cytotoxicity and higher transfection efficiency than PEI25kDa in transfecting miR-221/222 into rat Schwann cells (SCs). The upregulation of miR-221/222 in SCs promoted the expression of nerve growth factor and myelin basic protein in vitro. The mouse sciatic nerve crush injury model was used to evaluate the effectiveness of PDAPEI/miR-221/222 complexes for nerve regeneration in vivo. The results of electrophysiological tests, functional assessments, and histological and immunohistochemistry analyses demonstrated that PDAPEI/miR-221/222 complexes significantly promoted nerve regeneration after sciatic nerve crush, specificall

Published
2017

46. Polymerizing Pyrrole Coated Poly (l-lactic acid-co-ε-caprolactone) (PLCL) Conductive Nanofibrous Conduit Combined with Electric Stimulation for Long-Range Peripheral Nerve Regeneration

Author

Song, Jialin, primary, Sun, Binbin, additional, Liu, Shen, additional, Chen, Wei, additional, Zhang, Yuanzheng, additional, Wang, Chunyang, additional, Mo, Xiumei, additional, Che, Junyi, additional, Ouyang, Yuanming, additional, Yuan, Weien, additional, and Fan, Cunyi, additional

Published
2016
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49. Multifunctional Analgesic Sutures from Microfluidic Spinning Technology.

Author

Peng Y, Shang Y, Che J, Yu Y, Zhao Y, and Gu X

Abstract

Sutures are the most commonly used wound repair method after surgery. However, addressing delayed recovery and pain management remains a significant challenge. Here, microfibers are developed from microfluidic spinning with long-lasting analgesia capabilities for sutures. By using a solvent extraction manner, the polycaprolactone (PCL) microfibers encapsulated with ropivacaine (ROP), a well-known analgesic, can be continuously obtained from microfluidics. The intrinsic property of PCL and the advantage of microfluidic spinning technique impart the microfiber with highly controlled morphologies, mechanical strengths, as well as drug release. After exploring their biocompatibility both at in vitro and in vivo levels, the microfibers are directly applied to wound suture. The results demonstrate the lasting analgesic effect of the microfiber on mice with incision pain, highlighting its potential as promising suture for post-surgery treatments. It is anticipated that the multifunctional analgesic sutures produced through microfluidic spinning will pave the way for utilizing fibers as effective sutures in clinical incision wound treatment., (© 2024 Wiley‐VCH GmbH.)

Published
2024
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