Genetically engineered mannosylated-human serum albumin as a versatile carrier for liver-selective therapeutics

Hirata, Kenshiro; Maruyama, Toru; Watanabe, Hiroshi; Maeda, Hitoshi; Nakajou, Keisuke; Iwao, Yasunori; Ishima, Yu; Katsumi, Hidemasa; Hashida, Mitsuru; Otagiri, Masaki

doi:10.1016/j.jconrel.2010.03.010

Cited by 31 publications

(29 citation statements)

References 24 publications

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“…A pharmacokinetic analysis of the SH-Man-HSA showed that 50% of the administered dose was distributed to the liver within about 20 minutes, similar to previously reported findings for Man-HSA ( Fig. 2A) (Hirata et al, 2010). Furthermore, the hepatic distribution of SH-Man-HSA was investigated by means of a fluorescence-imaging technique.…”

Section: Resultssupporting

confidence: 85%

“…Our previous study revealed that Man-HSA was preferentially distributed to KC, but not to endothelial cells (Hirata et al, 2010). It has been demonstrated that the C-type lectin-like domain binds complex carbohydrates in which the chains are terminated with mannose, such as Man(n)GlcNAc2 (n, numbers of mannose residues).…”

Section: Resultsmentioning

confidence: 99%

“…The protocol used to express the recombinant HSAs (rHSAs), Man-HSA and HSA, by Pichia pastoris was a modification of a previously published procedure (Hirata et al, 2010). The eluted rHSAs were deionized and defatted by charcoal treatment, freeze-dried, and then stored at 280°C until used.…”

Section: Methodsmentioning

confidence: 99%

“…Using three HSA variantsAlbumin Dalakarlia, Casebrook, and Redhill )-as a template for designing a recombinant glycosylated-HSA, we recently succeeded, employing a yeast expression system, in producing a recombinant mannosylated-HSA (Man-HSA) containing a biosynthetic oligosaccharide chain with a high content of 12 mannose residues per HSA molecule (Supplemental Fig. 1) (Hirata et al, 2010). Therefore, Man-HSA would be anticipated to be efficiently distributed to CD68…”

Section: /Cd206mentioning

confidence: 99%

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Polythiol-Containing, Recombinant Mannosylated-Albumin Is a Superior CD68⁺/CD206⁺Kupffer Cell–Targeted Nanoantioxidant for Treatment of Two Acute Hepatitis Models

Maeda¹,

Hirata²,

Watanabe³

et al. 2014

J Pharmacol Exp Ther

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Since reactive oxygen species (ROS) derived from Kupffer cells (KC), especially CD681 KC, play a key role in the induction of hepatic oxidative stress and injuries, we developed a polythiolatedand mannosylated human serum albumin (SH-Man-HSA), which functions as a novel nanoantioxidant for delivering thiol to CD68 1 KC. In vitro electron paramagnetic resonance coupled with pharmacokinetics and immunohistochemical studies showed that SH-Man-HSA possessed powerful radical-scavenging activity and rapidly and selectively delivered thiols to the liver via mannose receptor (CD206) on CD68 1 cells. SH-Man-HSA significantly improved the survival rate of concanavalin-A (Con-A)-treated mice. Moreover, SH-Man-HSA exhibited excellent hepatoprotective functions, not by decreasing tumor necrosis factor or interferon-g production that is closely associated with Con-A-induced hepatitis, but by suppressing ROS production.Interestingly, the protective effect of SH-Man-HSA was superior to N-acetyl cysteine (NAC). This could be attributed to the difference in the inhibition of hepatic oxidative stress between the two antioxidants depending on their potential for thiol delivery to the liver. Similar results were also observed for acetaminophen (APAP)-induced hepatopathy models. Flow cytometric data further confirmed that an increase in F4/80 1 /ROS 1 cells was dramatically decreased by SH-Man-HSA. The administration of SH-Man-HSA at 4 hours following a Con-A or APAP injection also exhibited a profound hepatoprotective action against these hepatitis models, whereas this was not observed for NAC. It can be concluded therefore that SH-Man-HSA has great potential for use in a rescue therapy for hepatopathy as a nanoantioxidant because of its ability to efficiently and rapidly deliver thiols to CD68

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Section: Resultssupporting

confidence: 85%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: /Cd206mentioning

confidence: 99%

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Polythiol-Containing, Recombinant Mannosylated-Albumin Is a Superior CD68⁺/CD206⁺Kupffer Cell–Targeted Nanoantioxidant for Treatment of Two Acute Hepatitis Models

Maeda¹,

Hirata²,

Watanabe³

et al. 2014

J Pharmacol Exp Ther

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“…As mentioned in the section ''Carbohydrate (glycoprotein) receptor-mediated delivery'', the expression and endocytic capacity of the mannose/N-acetylglucosamine receptor are greater in LSECs than in Kupffer cells (Bijsterbosch et al, 1996;Kogelberg et al, 2007;Magnússon & Berg, 1993). However, the cellular uptake of mannose-mediated delivery systems depends on the amount and type of mannose molecules (Hirata et al, 2010;Jansen et al, 1991). For example, human serum albumin (HSA) terminated with seven para-aminophenyl mannose residues (Man7-HSA) is mainly taken up by Kupffer cells, but Man22-HSA and Man40-HSA are endocytosed by Kupffer cells and LSECs (Jansen et al, 1991).…”

Section: Carbohydrate (Glycoprotein) Receptor-mediated Deliverymentioning

confidence: 99%

Liver cell-targeted delivery of therapeutic molecules

Kang

Toita

Murata

2015

Critical Reviews in Biotechnology

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The liver is the largest internal organ in mammals and is involved in metabolism, detoxification, synthesis of proteins and lipids, secretion of cytokines and growth factors and immune/inflammatory responses. Hepatitis, alcoholic or non-alcoholic liver disease, hepatocellular carcinoma, hepatic veno-occlusive disease, and liver fibrosis and cirrhosis are the most common liver diseases. Safe and efficient delivery of therapeutic molecules (drugs, genes or proteins) into the liver is very important to increase the clinical efficacy of these molecules and to reduce their side effects in other organs. Several liver cell-targeted delivery systems have been developed and tested in vivo or ex vivo/in vitro. In this review, we discuss the literature concerning liver cell-targeted delivery systems, with a particular emphasis on the results of in vivo studies.

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Applications of Ligand‐Engineered Nanomedicines

Shim

Park

Roh

et al. 2013

Pharmaceutical Sciences Encyclopedia

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Over the past two decades, many therapeutic modalities have been investigated for the treatment of cancer. Among the most promising new modalities in the field of medical applications is nanomedicine, which has proven to be an outstanding approach for improving the therapeutic index. As this chapter will show, nanomedicines can achieve remarkable improvements in anticancer efficacy not only by increasing bioavailability and half‐life, but also by promoting tumor‐accumulation of therapeutic entities through the enhanced permeability and retention (EPR) effect. Moreover, through modifications of the surface of nanoparticles, nanomedicines have shown the ability to improve target‐specificity and further enhance the efficacy.

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Genetically engineered mannosylated-human serum albumin as a versatile carrier for liver-selective therapeutics

Cited by 31 publications

References 24 publications

Polythiol-Containing, Recombinant Mannosylated-Albumin Is a Superior CD68⁺/CD206⁺Kupffer Cell–Targeted Nanoantioxidant for Treatment of Two Acute Hepatitis Models

Polythiol-Containing, Recombinant Mannosylated-Albumin Is a Superior CD68⁺/CD206⁺Kupffer Cell–Targeted Nanoantioxidant for Treatment of Two Acute Hepatitis Models

Liver cell-targeted delivery of therapeutic molecules

Applications of Ligand‐Engineered Nanomedicines

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Genetically engineered mannosylated-human serum albumin as a versatile carrier for liver-selective therapeutics

Cited by 31 publications

References 24 publications

Polythiol-Containing, Recombinant Mannosylated-Albumin Is a Superior CD68+/CD206+Kupffer Cell–Targeted Nanoantioxidant for Treatment of Two Acute Hepatitis Models

Polythiol-Containing, Recombinant Mannosylated-Albumin Is a Superior CD68+/CD206+Kupffer Cell–Targeted Nanoantioxidant for Treatment of Two Acute Hepatitis Models

Liver cell-targeted delivery of therapeutic molecules

Applications of Ligand‐Engineered Nanomedicines

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Product

Resources

About

Polythiol-Containing, Recombinant Mannosylated-Albumin Is a Superior CD68⁺/CD206⁺Kupffer Cell–Targeted Nanoantioxidant for Treatment of Two Acute Hepatitis Models

Polythiol-Containing, Recombinant Mannosylated-Albumin Is a Superior CD68⁺/CD206⁺Kupffer Cell–Targeted Nanoantioxidant for Treatment of Two Acute Hepatitis Models