期刊
BIOACTIVE MATERIALS
卷 14, 期 -, 页码 120-133出版社
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2021.12.035
关键词
Mesoporous silica nanoparticles; Polyelectrolytes; Lubrication; Macrophage escape; Drug delivery
资金
- National Natural Science Foundation of China [52022043]
- Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research Program [20191080593]
- Capi-tal's Funds for Health Improvement and Research [2020-2Z-40810]
- Precision Medicine Foundation
- Tsinghua University, China [10001020107, 10001020120]
- Shanghai Collaborative Innovation Center for Translational Medicine [TM201802]
- Science and Tech-nology Commission of Shanghai Municipality [17140902500]
This study presents a lubricated nanocontainer for accurate drug delivery to the lesion while avoiding immune system recognition. Through in vitro and in vivo studies, this nanocontainer improves drug bioavailability and shows good biocompatibility.
Accurate drug delivery to the lesion has been deliberated for several decades, but one important phenomenon is usually neglected that the immune system can prevent smooth transportation of nanomedicine. Although injection would reduce first-pass effect, macrophages in the blood can still recognize and phagocytose nanomedicine. Here we show that a lubricated nanocontainer, which is prepared based on polyelectrolytes and mesoporous silica nanoparticles, can accurately target muscarinic bioreceptor while escaping from the identification of macrophages. Through in vitro and in vivo studies, this nanocontainer, combining both immune escape and bioreceptor targeting, has greatly improved the drug bioavailability. Additionally, this nanocontainer shows good biocompatibility, and the targeted heart tissues and other important metabolic organs, such as liver and kidney, keep physiological structures and functions without the detection of side effects. Furthermore, the mechanism of immune escape for the developed nanocontainer has been investigated by lubrication test and molecular simulation. We anticipate that our study will establish a new perspective on the achievement of immune escape-based targeted drug delivery, which can provide a fundamental approach for the design of related biomaterials.
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