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 - 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 - Porphyromonas gingivalis
KW - host immune dysfunction
KW - membrane cloaking nanoparticle
KW - periodontitis treatment
KW - responsive hydrogel
UR - http://www.scopus.com/inward/record.url?scp=85141020180&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85141020180&partnerID=8YFLogxK
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 -