TY - JOUR
T1 - Penetrating Macrophage-Based Nanoformulation for Periodontitis Treatment
AU - Yan, Na
AU - Xu, Junchao
AU - Liu, Guolin
AU - Ma, Chao
AU - Bao, Lin
AU - Cong, Yalin
AU - Wang, Ziyao
AU - Zhao, Yuliang
AU - Xu, Weihua
AU - Chen, Chunying
N1 - Funding Information:
We thank the Institute of Process Engineering for providing the CT equipment used for animal experiments. We also thank the Institute of Biophysics for providing equipment and technical support for high-resolution fluorescence microscopy (OMX-SIM) for bacterial imaging. This work was financially supported by the Ministry of Science and Technology of China (2021YFA1200900), the Major Instrument Project of the National Natural Science Foundation of China (22027810), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB36000000), the Innovative Research Groups of the National Natural Science Foundation of China (11621505), the Key-Area Research and Development Program of Guangdong Province (2019B090917011), and Guangdong High Level Innovation Research Institute (2020B0909010001).
Publisher Copyright:
© 2022 American Chemical Society. All rights reserved.
PY - 2022/11/22
Y1 - 2022/11/22
N2 - Periodontitis is a chronic inflammatory disease caused by the interaction of oral microorganisms with the host immune response. Porphyromonas gingivalis (P.g.) acts as a key mediator in subverting the homeostasis of the local immune system. On the one hand, P.g. inhibits phagocytosis and the killing capacity of immune cells. On the other hand, P.g. increases selective cytokine release, which is beneficial to its further proliferation. Here, we prepared a penetrating macrophage-based nanoformulation (MZ@PNM)-encapsulating hydrogel (MZ@PNM@GCP) that responded to the periodontitis microenvironment. MZ@PNM targeted P.g. via the Toll-like receptor complex 2/1 (TLR2/1) on its macrophage-mimicking membrane, then directly killed P.g. through disruption of bacterial structural integrity by the cationic nanoparticles and intracellular release of an antibacterial drug, metronidazole (MZ). Meanwhile, MZ@PNM interrupted the specific binding of P.g. to immune cells and neutralized complement component 5a (C5a), preventing P.g. subversion of periodontal host immune response. Overall, MZ@PNM@GCP showed potent efficacy in periodontitis treatment, restoring local immune function and killing pathogenic bacteria, while exhibiting favorable biocompatibility, all of which have been demonstrated both in vivo and in vitro.
AB - Periodontitis is a chronic inflammatory disease caused by the interaction of oral microorganisms with the host immune response. Porphyromonas gingivalis (P.g.) acts as a key mediator in subverting the homeostasis of the local immune system. On the one hand, P.g. inhibits phagocytosis and the killing capacity of immune cells. On the other hand, P.g. increases selective cytokine release, which is beneficial to its further proliferation. Here, we prepared a penetrating macrophage-based nanoformulation (MZ@PNM)-encapsulating hydrogel (MZ@PNM@GCP) that responded to the periodontitis microenvironment. MZ@PNM targeted P.g. via the Toll-like receptor complex 2/1 (TLR2/1) on its macrophage-mimicking membrane, then directly killed P.g. through disruption of bacterial structural integrity by the cationic nanoparticles and intracellular release of an antibacterial drug, metronidazole (MZ). Meanwhile, MZ@PNM interrupted the specific binding of P.g. to immune cells and neutralized complement component 5a (C5a), preventing P.g. subversion of periodontal host immune response. Overall, MZ@PNM@GCP showed potent efficacy in periodontitis treatment, restoring local immune function and killing pathogenic bacteria, while exhibiting favorable biocompatibility, all of which have been demonstrated both in vivo and in vitro.
KW - host immune dysfunction
KW - membrane cloaking nanoparticle
KW - periodontitis treatment
KW - Porphyromonas gingivalis
KW - responsive hydrogel
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U2 - 10.1021/acsnano.2c05923
DO - 10.1021/acsnano.2c05923
M3 - Article
C2 - 36288552
AN - SCOPUS:85141020180
SN - 1936-0851
VL - 16
SP - 18253
EP - 18265
JO - ACS Nano
JF - ACS Nano
IS - 11
ER -