An Overview of Drug Delivery Nanosystems for Sepsis-Related Liver Injury Treatment

Figures & data

Figure 1 Pathogenesis of sepsis-related liver injury and drug delivery nanosystems.

Figure 2 Mechanism of DOX-hyd-BSA NPs targeting pro-inflammatory neutrophils to induce their apoptosis for the treatment of septic inflammation. (A) The therapeutic mechanism of DOX-hyd-BSA NPs; (B) The preparation route of DOX-conjugated BSA NPs.

Notes: Reprinted from Zhang CY, Dong X, Gao J, Lin W, Liu Z, Wang Z. Nanoparticle-induced neutrophil apoptosis increases survival in sepsis and alleviates neurological damage in stroke. Sci Adv. 2019;5(11):eaax7964. https://creativecommons.org/licenses/by-nc/4.0/.³⁴

Figure 3 Scheme for designing IME responsive and biofunctional nanoparticles (NPs) and for targeted delivery of nanotherapeutics at the site of infection. (A) The designing strategy of intercellular adhesion molecule-1 antibodies-modified multifunctional NPs; (B) The prepared NPs showed a preferential accumulation at a site of infection by interaction with intercellular adhesion molecule-1.

Notes: Reprinted with permission from John Wiley and Sons. Zhang CY, Gao J, Wang Z. Bioresponsive nanoparticles targeted to infectious microenvironments for sepsis management. Adv Mater. 2018;30(43):e1803618. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.⁵⁵

Table 1 Antioxidant Nanodrug Delivery System with Potential to Alleviate Liver Injury in Sepsis

Name	Acting Cell/Site	Advantages	Loaded Drugs	Animal Models	Particle Size	Shape	References
CNPs	Hepatocytes	Improved the survival rate, reduced systemic and hepatic oxidative stress as well as serum cytokine/chemokine levels.	CeO	Rats	10–30nm	Cubic fluorite structure	[76]
CZ NPs	Hepatocytes	Possessed a higher Ce^3+ /Ce^4+ ratio and faster conversion from Ce^4+ to Ce^3+	CeO	Rats	2–4nm	Fluorite structure	[77]
CeO2 NPs	Hepatocytes	Reduced levels of nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and decreased nuclear factor-kappa light chain enhancer of activated B cells (NF-kB) transcriptional activity.	CeO2	Mice	200–400 nm	Spherical	[78]
Atv/PTP-TCeria NPs	Mitochondria	Targeted mitochondria to eliminate excessive ROS	CeO2	Mice	30–80 nm	Spherical	[71]
AgNPs	Liver	Reduced ROS and RNS production	Ag	Rats	10–200nm	Spherical	[79]
Nanosheets	Mitochondria	Reduced ROS and RNS production	WS2, MoSe2, and WSe2	Rats	37.5 nm	Nanosheets	[80]
PCM-MSN@LA	Liver	Increased the activity of myocardial cells, down-regulated the expression of inflammatory factors and the production of ROS, alleviated cardiac insufficiency in sepsis	MSN	Rats	-	-	[81]
RNP^N NPs	Multiple organs	Improved pharmacological performance dramatically reduced the radiation-induced organ dysfunctions and increased the survival time of the lethally irradiated mice irradiated mice	RNP^N	Rats	-	-	[82]
mSPAM	Macrophages	Suppressed HIF1α expression in LPS-stimulated macrophages and thereby inhibited the progression of local and systemic inflammation	BM	A local endotoxemia animal model	97nm	Spherical	[83]
PEG-BR@SPIONs	Whole body	Had the potential of the biosensors for ROS detection and could be used to diagnose many diseases associated with ROS overproduction.	PEG-BR	Rats	15nm	Ridge-tile	[84]
Nano-CuO	Mitochondria	Triggered oxidative stress by ROS, which in turn resulted in activation of ER stress pathways causing cell death in liver tissue and BRL-3A cells.	CuO	Male Wistar rats	20–40um	Hexagonal	[85]
TiO2 NPs	Hepatocytes	Had cytotoxic effects on the intestine and liver structure and function by inducing oxidative stress, inflammation, and apoptosis.	TiO2	Male rats	30nm	Spherical	[86]

Figure 4 Preparation and efficacy assessment of PEG-HNPs for sepsis treatment.

Notes: Reprinted from Koide H, Okishima A, Hoshino Y, et al. Synthetic hydrogel nanoparticles for sepsis therapy. Nat Commun. 2021;12(1):5552. https://creativecommons.org/licenses/by/4.0/.⁴⁴

Table 2 Summary of Drug Delivery Nanosystems for Bacterial Translocation in SRIL

Drug Delivery Nanosystem	Active Substance	Classification of Pathogens	Results	References
Spherical silver nanoparticle	Ag	Gram-positive and Gram-negative bacteria	Strong killing power for Klebsiella pneumoniae	[98]
The porous structure of MSNs nanoparticle	Meropenem	Carbapenem-resistant Enterobacteriaceae.	Desirable biocompatibility, low cytotoxicity and the improved antibacterial effect	[102]
Uniform rod-like morphology nanoparticle	Genistein	Apoptosis-associated plaque-like protein containing a CARD (ASC) and Caspase1-p20	Modulated the gut microbiota, and alleviated colitis.showed excellent safety	[103]
Vitamin C lipid nanoparticles	MACs	Multidrug-resistant bacteria, including Staphylococcus aureus and Escherichia coli	The elimination of multidrug-resistant bacteria, including Staphylococcus aureus and Escherichia coli, leading to the complete recovery of immunocompromised septic mice	[104]
Ångstrom-scale silver nanoparticles (F-AgÅPs)	AgÅPs	Multi-drug resistant Staphylococcus aureus (S. aureus)- and Escherichia coli (E. coli)	Reduced bacterial burden, reversed dysregulated inflammation, and enhanced survival in mice with CLP - or E. coli bloodstream infection- induced sepsis	[105]
Lipase-sensitive polymeric triple-layered nanogel (TLN)	Lipase	Staphylococcus aureus (S. aureus)	Inhibiting S. aureus growth,released the drug to kill intracellular bacteria	[53]
Spherical nanoparticle	TiO2 NPs	Lactobacillus_reuteri	Induced slight hepatotoxicity at dose of 50 mg/kg after long-term oral exposure.The indirect pathway of the gut-liver axis, linking liver metabolism and gut microbiota	[86]

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