Understanding the Potential Role of Nanotechnology in Liver Fibrosis: A Paradigm in Therapeutics
Abstract
:1. Introduction
2. Epidemiology of Chronic Liver Diseases
3. Pathogenesis and Pathophysiology of Liver Fibrosis
4. Evidence of Liver Fibrosis Progression and Regression
4.1. Liver Fibrosis Progression: Upregulation in Fibrolytic Activity
4.2. Liver Fibrosis Regression: Cell Apoptosis or Downregulation of Hepatic Stellate Cells
5. Clinical Evaluation of Liver Fibrosis
5.1. Pharmacological Elements of Liver
5.2. Paramedical Evaluation of Liver Fibrosis
5.3. Nanotechnology-Based Diagnosis of Liver Fibrosis
6. Synthetic Therapeutic Agents for Liver Fibrosis Management
6.1. Hepatic Stellate Cells-Targeting Potential Substances and Extracellular Matrix-Interfering Modulators
6.2. Hepatoprotective Agents
6.3. Anti-Inflammatory and Antioxidant Therapies
7. Role of Nanotechnology in Liver Fibrosis Therapy Using Synthetic Drugs
8. Emerging Perspectives of Herbal Compounds in Liver Fibrosis Therapy
8.1. Epigallocathechin-3-gallate (EGCG)
8.2. Silymarin
8.3. Oxymatrine
8.4. Curcumin
8.5. Tetrandrine
8.6. Glycyrrhetinic Acid
8.7. Salvianolic Acid
8.8. Plumbagin
8.9. Scutellara Baicalnsis Georgi
8.10. Astragalosides
8.11. Hawthorn Extract
8.12. Andrographolides
9. Role of Nanotechnology in Liver Fibrosis Therapy Using Herbal Compounds
10. Conclusions and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
α-SMA | Alpha-smooth muscle actin |
ACE | Angiotensin-converting enzyme |
AFP | Alpha-fetoprotein |
ALP | Alkaline phosphatase |
ALT | Alanine aminotransferase |
API | Active pharmaceutical ingredient |
ASK-1 | Apoptosis-signal regulating kinase-1 |
AST | Aspartate aminotransferase |
CAT | Catalase |
CB1 | Cannabinoid receptor type 1 |
CCL2 | Chemokine |
CCl4 | Carbon tetrachloride |
CLDs | Chronic liver diseases |
COX | Cyclooxygenase |
CRMs | Cis-acting regulatory modules |
CTGF | Connective tissue growth factor |
DCs | Dendritic cells |
DSPE | 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine |
ECM | Extracellular matrix |
EGCG | Epigallocathechin-3-gallate |
EGFR | Epidermal growth factor receptor |
EMT | Epithelial-mesenchymal transition |
GM-CT-01 | Galactomannan |
GR-MD-02 | Galactoarabino-rhamnogalaturonan |
GSH | Glutathione |
HCC | Hepatocellular carcinoma |
HCV | Hepatitis C virus |
HSCs | Hepatic stellate cells |
IL-1 | Interleukins-1 |
IL-2 | Interleukins-2 |
IL-13 | Interleukin-13 |
JNK | c-Jun N-terminal kinases |
LOXL2 | Lysyl oxidase-like 2 |
LPO | Lipid peroxidation |
MAPK | Mitogen-activated protein kinase |
MDA | Malonaldehyde |
MFBs | Myofibroblasts |
MMP-1 | Matrix metalloproteinase-1 |
MRI | Magnetic resonance imaging |
NASH | Non-alcoholic steatohepatitis |
NFkB | Nuclear factor kappa-light-chain-enhancer of activated B cells |
NLCs | Nanostructured lipid carriers |
Nrf2 | Nuclear factor erythroid 2–related factor 2 |
OM | Oxymatrine |
PPARs | Peroxisome proliferator active receptors |
PDGF | Platelet-derived growth factor |
PDGFR | Platelet derived growth factor receptor |
PS | Phosphatidylserine |
ROS | Reactive oxygen species |
SAB@MSNs-RhB | Rhodamine B covalently grafted salvianolic acid B-loaded mesoporous silica nanoparticles |
TGF-β | Transforming growth factor-β |
TIMP-1 | Tissue inhibitor metalloproteinase-1 |
TLRs | Toll-like receptors |
TNF-ɑ | Tumor necrosis factor-ɑ |
TRAIL | Tumor necrosis (TNF)-related apoptosis-inducing ligands |
VEGF | Vascular endothelial growth factor |
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Nanoparticle Type | Nanoparticle Subtype | Drug | Targeted Ligands | Targeted Biological Structures | Ref. |
---|---|---|---|---|---|
Polymeric NPs | Poly lactic co glycolic b poly(ethylene glycol) maleimide micelle | Nilotinib | Collagenase I and retinol | Hepatic stellate cell | [97] |
Diblock copolymers (POEGMA-b-VDM) | S-nitrosoglutathione | Vitamin A | Hepatic stellate cell | [98] | |
Poly (lactic-co-glycolic acid) NPs | Spleen tyrosine kinase inhibitor (R406) | R406 | Macrophages | [99] | |
Retinol conjugated polyetherimine nanoparticle | Antisense oligonucleotide (DNA oligomers) | Retinol conjugated polyetherimine | Hepatic stellate cell | [100] | |
Retinol-chitosan NPs | Atorvastatin and JQ1 (which is thienotriazolodiazepine and acts as selective inhibitor of Bromodomain-containing Protein 4 signaling pathway) | Vitamin A | Hepatic stellate cell | [101] | |
Inorganic NPs | Erlotinib-loaded myofibroblast-targeting nanoparticles | Erlotinib | Epidermal growth factor receptor | Hepatic sinusoids | [102] |
Lipid based NPs | Liposomes | Imatinib | Vitamin A | Hepatic stellate cell | [103] |
Liposomes | Valsartan | Vitamin A | Hepatic stellate cell | [104] | |
Liposomes | Antiangiogenic siRNA | Vascular endothelial growth factor siRNA (Small interfering RNA) | Hepatic stellate cell | [91] |
Type of Nanoparticles (NPs) | NPs as Drug Carrier | Drug | Ref. |
---|---|---|---|
Lipid based NPs | RNA oligonucleotide liposomal | MTL-CEBPA (saRNA) | [114] |
Liposomes | Dexamethasone | [118] | |
Cationic lipid NPs | Small interfering ribose nucleic acid to the procallogen 1 (I) gene | [115] | |
Inorganic NPs | Poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) | Sorafenib | [119] |
Iron oxide nanoparticles | Citrate | [54] | |
Calcium phosphate NPs | Tumor necrosis factor-stimulated gene 6 | [120] | |
Polymeric NPs | Ketal cross-linked cationic nanohydrogel | Cy5-labeled anti-col1α1 siRNA | [117] |
Cationic nanohydrogel particles | Anti-col1α1 siRNA | [121] | |
Protein NPs | Polyavidin-based NPs | Dexamethasone | [122] |
Albumin NPs | Dexamethasone | [123] |
Phytoconstituent | Inference | Ref. |
---|---|---|
Salvianolic acid B | According to the study, SAB@MSNs-RhB had significantly greater sustained-release capability than SAB@MSNs and displayed higher release rates and concentrations in the sustained release pattern beyond 96 h. These nanoparticles also improved cellular drug uptake, bioaccessibility, higher efficacy in suppressing reactive oxygen species levels, and management of hepatic fibrosis. | [204] |
Curcumin | The results of the study showed that curcumin platinum nanoparticles had greater activity at concentrations of 1.5 and 1.25 g/mL, causing the viability of NIH3T3 cells to significantly decline to 44.06% and 48.96%, respectively, for decreasing collagen production by NIH3T3 fibroblast cell line, making them a suitable candidate for hepatic fibrosis. | [205] |
Phyllanthin | The results of the study demonstrated that Phyllanthin nanoparticles could reverse the biochemical and histological alterations brought on by the hepatotoxin and produced a therapeutic effect at a dose of 5 mg/kg body weight, which was half the dose of conventional medication in carbon tetrachloride (CCl4)-induced fibrotic model. | [206] |
Silymarin | The study looked at the effects of silymarin-loaded Eudragit RS100 nanoparticles for hepatoprotective and anti-fibrotic benefits of silymarin in cholestatic liver fibrosis, which acts by restoring liver function through antioxidant activity, which eventually leads to enhancement in anti-fibrotic effect in bile duct ligation induced fibrotic model. | [207] |
Curcumin | According to the study, the bioavailability of the drug in curcumin-loaded zein nanospheres increased by 3.24 times when compared to the free solution, making them an ideal carrier for enhanced liver targeting and anti-fibrotic effectiveness in CCl4-induced fibrotic models. | [208] |
Berberine | The study demonstrated that berberine-loaded bovine serum albumin nanoparticles decreased LX-2 cell growth and showed stronger caspase 3 activations at a lower dosage in comparison to free drugs. These nanoparticles exhibited drug release of 80% in 72 h, demonstrating sustained drug release. Berberine-loaded NPs provided hepatoprotection in CCl4-induced hepatotoxicity. | [209] |
San-Huang-Xie-Xin-Tang (SHXXT) decoction | The research results showed that nanoformulation of SHXXT decoction had remarkable healing potential, as evident through a reduction in AST and ALT levels in liver injury in the chloroform-induced liver fibrotic model. | [210] |
Naringenin | According to the study, naringenin-loaded solid lipid nanoparticles significantly decreased CCl4-induced liver fibrosis through a decrease in biochemical markers, including serum ALP, AST, and total bilirubin, as well as pro-inflammatory markers such as TNF-, IL1β, and IL-6. In addition, pro-MMP-2 and MMP-2 activation in the HSCs were enhanced by naringenin-SLN. | [211] |
Curcumin | The results of the study showed that nano-curcumin nano-chitosan mixtures had considerable hepatoprotective action through regulation of the liver enzymes ALT, AST, and ALP; AFP; caspase-3; oxidative stress biomarker such as malondialdehyde; antioxidant biomarkers such as glutathione and catalase in CCl4-induced liver fibrosis in mice model. | [212] |
Hesperidin | The study’s findings demonstrated that, in contrast to hesperidin alone, DSPE-SPE-sebacic acid conjugated liposomes loaded with hesperidin provided selective targeting of HSCs in CCL4-induced rat liver fibrosis. This was demonstrated by a significant reduction in serum ALT, AST, and ALP activities as well as albumin levels. | [213] |
Curcumin | In CCl4-induced liver fibrosis in rats, phosphatidylserine-modified-NLCs loaded with curcumin selectively targeted hepatic macrophages as demonstrated by their highest concentration in the liver. These nanoparticles upregulated the levels of hepatocyte growth factors and matrix metalloprotease while downregulating the amounts of collagen fibers and alpha-smooth muscle actin. They also enhanced the levels of liver enzymes and pro-inflammatory cytokines in blood circulation. | [214] |
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Singh, S.; Sharma, N.; Shukla, S.; Behl, T.; Gupta, S.; Anwer, M.K.; Vargas-De-La-Cruz, C.; Bungau, S.G.; Brisc, C. Understanding the Potential Role of Nanotechnology in Liver Fibrosis: A Paradigm in Therapeutics. Molecules 2023, 28, 2811. https://doi.org/10.3390/molecules28062811
Singh S, Sharma N, Shukla S, Behl T, Gupta S, Anwer MK, Vargas-De-La-Cruz C, Bungau SG, Brisc C. Understanding the Potential Role of Nanotechnology in Liver Fibrosis: A Paradigm in Therapeutics. Molecules. 2023; 28(6):2811. https://doi.org/10.3390/molecules28062811
Chicago/Turabian StyleSingh, Sukhbir, Neelam Sharma, Saurabh Shukla, Tapan Behl, Sumeet Gupta, Md. Khalid Anwer, Celia Vargas-De-La-Cruz, Simona Gabriela Bungau, and Cristina Brisc. 2023. "Understanding the Potential Role of Nanotechnology in Liver Fibrosis: A Paradigm in Therapeutics" Molecules 28, no. 6: 2811. https://doi.org/10.3390/molecules28062811
APA StyleSingh, S., Sharma, N., Shukla, S., Behl, T., Gupta, S., Anwer, M. K., Vargas-De-La-Cruz, C., Bungau, S. G., & Brisc, C. (2023). Understanding the Potential Role of Nanotechnology in Liver Fibrosis: A Paradigm in Therapeutics. Molecules, 28(6), 2811. https://doi.org/10.3390/molecules28062811