posted on 2024-01-16, 10:33authored byHuan Cao, Jianhua Zhang, Lei Yang, Haotian Li, Rong Tian, Haoxing Wu, Yiwen Li, Zhipeng Gu
Apart
from bacterial growth and endotoxin generation, the excessive
production of reactive radicals linked with sepsis also has a substantial
impact on triggering an inflammatory response and further treatment
failure. Hence, the rational design and fabrication of robust and
multifunctional nanoparticles (NPs) present a viable means of overcoming
this dilemma. In this study, we used antibiotic polymyxin B (PMB)
and antioxidant natural polyphenolic protocatechualdehyde (PCA) to
construct robust and multifunctional NPs for sepsis treatment, leveraging
the rich chemistries of PCA. The PMB release profile from the NPs
demonstrated pH-responsive behavior, which allowed the NPs to exhibit
effective bacterial killing and radical scavenging properties. Data
from in vitro cells stimulated with H2O2 and lipopolysaccharide (LPS) showed the multifunctionalities
of NPs, including intracellular reactive oxygen species (ROS) scavenging,
elimination of the bacterial toxin LPS, inhibiting macrophage M1 polarization,
and anti-inflammation capabilities. Additionally, in vivo studies further demonstrated that NPs could increase the effectiveness
of sepsis treatment by lowering the bacterial survival ratio, the
expression of the oxidative marker malondialdehyde (MDA), and the
expression of inflammatory cytokine TNF-α. Overall, this work
provides ideas of using those robust and multifunctional therapeutic
NPs toward enhanced sepsis therapy efficiency.