大鼠气溶胶给药器

Autologous Skin Fibroblast-Based PLGA Nanoparticles for
Treating Multiorgan Fibrosis
Qiang Long, Zehua Liu, Qianwen Shao, Hongpeng Shi, Shixing Huang, Chenyu Jiang,
Bei Qian, Yiming Zhong, Xiaojun He, Xiaogang Xiang, Yang Yang, Bing Li, Xiaoxiang Yan,
Qiang Zhao,* Xiaoli Wei,* Hélder A. Santos,* and Xiaofeng Ye*
Fibrotic diseases remain a substantial health burden with few therapeutic
approaches. A hallmark of fibrosis is the aberrant activation and accumulation
of myofibroblasts, which is caused by excessive profibrotic cytokines.
Conventional anticytokine therapies fail to undergo clinical trials, as simply
blocking a single or several antifibrotic cytokines cannot abrogate the
profibrotic microenvironment. Here, biomimetic nanoparticles based on
autologous skin fibroblasts are customized as decoys to neutralize multiple
fibroblast-targeted cytokines. By fusing the skin fibroblast membrane onto
poly(lactic-co-glycolic) acid cores, these nanoparticles, termed fibroblast
membrane-camouflaged nanoparticles (FNPs), are shown to effectively
scavenge various profibrotic cytokines, including transforming growth
factor-휷, interleukin (IL)-11, IL-13, and IL-17, thereby modulating the
profibrotic microenvironment. FNPs are sequentially prepared into multiple
formulations for different administration routines. As a proof-of-concept, in
three independent animal models with various organ fibrosis (lung fibrosis,
liver fibrosis, and heart fibrosis), FNPs effectively reduce the accumulation of
myofibroblasts, and the formation of fibrotic tissue, concomitantly restoring
organ function and indicating that FNPs are a potential broad-spectrum
therapy for fibrosis management.
Q. Long, H. Shi, S. Huang, C. Jiang, B. Qian, Y. Zhong, X. He, Q. Zhao,
X. Ye
Department of Cardiovascular Surgery
Ruijin Hospital
Shanghai Jiao Tong University School of Medicine
Shanghai 200025, China
E-mail: zq11607@rjh.com.cn; yxf11612@rjh.com.cn
Z. Liu, H. A. Santos
Department of Biomedical Engineering, W.J. Kolff Institute for
Biomedical Engineering and Materials Science
University Medical Center Groningen/University of Groningen
Ant. Deusinglaan 1, Groningen 9713 AV, The Netherlands
E-mail: h.a.santos@umcg.nl
The ORCID identification number(s) for the author(s) of this article
can be found under https://doi.org/10.1002/advs.202200856
© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.
This is an open access article under the terms of the Creative Commons
Attribution License, which permits use, distribution and reproduction in
any medium, provided the original work is properly cited.
DOI: 10.1002/advs.202200856
1. Introduction
Fibrosis, or disordered fibrotic tissue formation, is characterized by the abnormal
fibroblast activation that induces excessive extracellular matrix (ECM) remodeling
and primarily accounts for multiple organ
dysfunctions.[1] The pervasive occurrence
of fibrosis in almost all diseases generates
a large healthcare burden worldwide. However, the clinical benefits of antifibrotic therapy through small molecules, such as pirfenidone and nintedanib, are usually offset
by their modest therapeutic efficacy, limited
indications and severe side effects.[2] Therefore, alternative clinical intervention modalities to target fibrosis are urgently needed.
Considering the central role of myofibroblast activation and proliferation in
fibrosis establishment,[3] recent breakthroughs have focused on the ablation
of progressive myofibroblast activation
through autologous cell-based therapy.
For example, autologous chimeric antigen
Z. Liu, H. A. Santos
Drug Research Program
Division of Pharmaceutical Chemistry and Technology
Faculty of Pharmacy
University of Helsinki
Helsinki FI-00014, Finland
Q. Shao, X. Wei
Department of Pharmacology
School of Basic Medical Sciences
Fudan University
Shanghai 200032, China
E-mail: xlwei@fudan.edu.cn
X. Xiang
Department of Infectious Diseases
Ruijin Hospital
Shanghai Jiao Tong University School of Medicine
Shanghai 200025, China
Y. Yang
Department of Thoracic Surgery
Shanghai Pulmonary Hospital
School of Medicine
Tongji University
Shanghai 200000, China
Adv. Sci. 2022, 9, 2200856 2200856 (1 of 14) © 2022 The Authors. Advanced Science published by Wiley-VCH GmbH