An integrin-based nanoparticle that targets activated hepatic stellate cells and alleviates liver fibrosis

Li, Yanping; Pu, Shiyun; Liu, Qinhui; Li, Rui; Zhang, Jinhang; Wu, Tong; Chen, Lei; Li, Hong; Yang, Xuping; Zou, Min; Xiao, Jiumei; Xie, Wen; He, Jinhan

doi:10.1016/j.jconrel.2019.04.022

Cited by 65 publications

(60 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a mouse model of hepatic fibrosis, cyclic peptide-guided liposomes preferentially targeted the activated hepatic stellate cells (not quiescent ones) to treat the fibrotic phenotype (102). α v β 3 antagonists are being tried for the inhibition of retinal neovascularization and may have therapeutic value in ROP (89).…”

Section: Integrin-targeted Therapiesmentioning

confidence: 99%

The role of integrins in inflammation and angiogenesis

2020

View full text Add to dashboard Cite

Integrins are heterodimeric transmembrane cell adhesion molecules made up of alpha (α) and beta (β) subunits arranged in numerous dimeric pairings. These complexes have varying affinities to extracellular ligands. Integrins regulate cellular growth, proliferation, migration, signaling, and cytokine activation and release and thereby play important roles in cell proliferation and migration, apoptosis, tissue repair, as well as in all processes critical to inflammation, infection, and angiogenesis. This review presents current evidence from human and animal studies on integrin structure and molecular signaling, with particular emphasis on signal transduction in infants. We have included evidence from our own laboratory studies and from an extensive literature search in databases PubMed, EMBASE, Scopus, and the electronic archives of abstracts presented at the annual meetings of the Pediatric Academic Societies. To avoid bias in identification of existing studies, key words were short-listed prior to the actual search both from anecdotal experience and from PubMed’s Medical Subject Heading (MeSH) thesaurus. Impact Integrins are a family of ubiquitous αβ heterodimeric receptors that interact with numerous ligands in physiology and disease. Integrins play a key role in cell proliferation, tissue repair, inflammation, infection, and angiogenesis. This review summarizes current evidence from human and animal studies on integrin structure and molecular signaling and promising role in diseases of inflammation, infection, and angiogenesis in infants. This review shows that integrin receptors and ligands are novel therapeutic targets of clinical interest and hold promise as novel therapeutic targets in the management of several neonatal diseases.

show abstract

Section: Integrin-targeted Therapiesmentioning

confidence: 99%

The role of integrins in inflammation and angiogenesis

2020

View full text Add to dashboard Cite

show abstract

“…KCs and LSECs specifically recognize oxidized low-density lipoprotein, human serum albumin (HSA), and negatively charged NPs by scavenger receptors, while hepatocytes are more likely to take up NPs with positive surface charge. According to the mentioned data in Table 1 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , almost all of drug-loaded NPs for liver fibrosis possess a negative charge which is in favor of KCs and LSECs, while the most favored cells in fibrosis targeting seem to be HSCs. Even though current therapies are not sufficient enough to completely cure of hepatic fibrosis, numerous drugs which include pioglitazone, obeticholic acid, losartan, candesartan, glycyrrhizin, pentoxifylline, everolimus, and simtuzumab have been registered/continued in clinical trials 34 , 35 ( Table 2 ), and at the same time, lipid- and polymer-based drug delivery carriers have gained much more attention for targeting liver fibrosis 36 ( Table 1 ).…”

Section: Rational Therapeutic Measuresmentioning

confidence: 99%

“… Carrier Drug Targeting agent Size (nm) Zeta potential (mV) Effect and mechanism of action Ref. Bovine serum albumin Berberine – 394.9 ± 102.03 ‒30 to 30 The LX-2 cell growth inhibition, stronger CASP3 activation at lower dose, and in vivo anti-hepatotoxicity effect at 1 and 2 μg/g 21 Bovine serum albumin Sodium ferulate M6P 100 to 200 −2.73 to −35.85 Specific uptake by HSC (less distribution to the kidneys), slower elimination rate, and much higher drug concentration 23 Liposome Vismodegib Cyclic peptides (cRGDyK) 75.6 ± 2.4 −24.8 ± 1.8 Inhibited hedgehog pathway signaling in HSCs, and alleviated hepatotoxin-induced fibrosis in mice 24 M6P-HSA-conjugated liposome Rosiglitazone M6P-HSA 135.1 ± 3.74 −30.5 ± 2.64 Increased liver uptake (2.61-fold), improved biochemical markers level and histopathological morphology, and decreased fibrosis grade 25 cRGD-modified liposome (IFN)- α 1b cRGD 101 ± 17 .7 – Reduction in the extent of liver fibrosis in BDL rats 26 Liposome IFN- γ Cyclic peptides ≤100 – Extended circulation half-life, reduced side-effects in rats with hepatic fibrosis due to selective delivery to activated HSCs 27 Mesoporous silica NPs-RhB Salvianolic acid B – 400 – Remarkable inhibiting effect on reactive oxygen species level and on the proliferation activity of LX-2 cells 28 NLC Curcumin Phosphatidylserine 204.6 ± 1.97 −46.29 ± 0.48 Prolonged retention time, and enhanced bioavailability and delivery efficiency …”

Section: Rational Therapeutic Measuresmentioning

confidence: 99%

Efficient drug and gene delivery to liver fibrosis: rationale, recent advances, and perspectives

Mahdinloo

Kiaie

Amiri

et al. 2020

Acta Pharmaceutica Sinica B

View full text Add to dashboard Cite

Liver fibrosis results from chronic damages together with an accumulation of extracellular matrix, and no specific medical therapy is approved for that until now. Due to liver metabolic capacity for drugs, the fragility of drugs, and the presence of insurmountable physiological obstacles in the way of targeting, the development of efficient drug delivery systems for anti-fibrotics seems vital. We have explored articles with a different perspective on liver fibrosis over the two decades, then collected and summarized the information by providing corresponding in vitro and in vivo cases. We have discussed the mechanism of hepatic fibrogenesis with different ways of fibrosis induction in animals. Furthermore, the critical chemical and herbal anti-fibrotics, biological molecules such as micro-RNAs, siRNAs, and growth factors, which can affect cell division and differentiation, are mentioned. Likewise, drug and gene delivery and therapeutic systems on in vitro and in vivo models are summarized in the data tables. This review article enlightens recent advances in emerging drugs and nanocarriers and represents perspectives on targeting strategies employed in liver fibrosis treatment.

show abstract

“…The results demonstrated attenuation of advanced liver fibrosis model in mice. [ 24 ] In addition to small molecular inhibitors, genetic studies confirmed the activation of HH pathway via the overexpression of smoothened homolog (SMO) and sonic hedgehog (SHH) signaling molecule genes or the underexpression of the gene encoding hedgehog interacting protein (HHIP). [ 20 ] The former genes offer potential candidates for gene therapy.…”

Section: Gene Targets Involved In the Treatment Of Hccmentioning

confidence: 99%

Gene Therapy for Hepatocellular Carcinoma: Highlighting the Journey from Theory to Clinical Applications

Younis

Khalil

Harashima

2020

Advanced Therapeutics

View full text Add to dashboard Cite

Treatment for hepatocellular carcinoma (HCC) is currently limited to early stages where surgical intervention is applicable. Meanwhile, the response for most chemotherapies is still low, leaving patients in advanced stages without an effective therapeutic approach. Other therapeutic strategies based on immunotherapies or radiotherapy have a narrow spectrum with multiple limitations. These collective drawbacks necessitate the development of alternative strategies. Gene therapy has achieved a breakthrough in the treatment of several diseases, especially tumors. In the current review, a discussion is provided on the various strategies that have been developed for HCC gene therapy, the functional and genetic materials used, and their diverse delivery systems, with a special focus on novel targeting strategies based on biomaterials, peptide libraries, and aptamers. In addition, animal models that have been used in preclinical evaluation of HCC gene therapies are highlighted and compared. Lastly, ongoing clinical trials and future perspectives for these strategies are discussed.

show abstract

An integrin-based nanoparticle that targets activated hepatic stellate cells and alleviates liver fibrosis

Cited by 65 publications

References 37 publications

The role of integrins in inflammation and angiogenesis

The role of integrins in inflammation and angiogenesis

Efficient drug and gene delivery to liver fibrosis: rationale, recent advances, and perspectives

Gene Therapy for Hepatocellular Carcinoma: Highlighting the Journey from Theory to Clinical Applications

Contact Info

Product

Resources

About