Lymphatic targeting by albumin-hitchhiking: Applications and optimisation

Abdallah, Mohammad; Müllertz, Olivia; Styles, Ian K.; Mörsdorf, Alexander; Quinn, John F.; Whittaker, Michael R.; Trevaskis, Natalie L.

doi:10.1016/j.jconrel.2020.07.046

Cited by 69 publications

(50 citation statements)

References 154 publications

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“…For albumin, we investigated protein binding to its cognate neonatal receptor, FcRn and observed that regardless of protein glycosylation degree, binding constants remained very similar (Figure 2A). Natural capacity of albumin to bind hydrophobic substrates, which is widely used as a tool of drug delivery to extend circulation lifetime of drugs and/or to achieve lymphoid drug targeting, [34] was also unperturbed by surface glycosylation: dansyl‐labelled arginine and sarcosine exhibited quantitatively similar binding profiles to Sudlow I and II hydrophobic binding pockets of albumin, respectively, [35] irrespective of the extent of glycosylation (Figure 2B for dansyl sarcosine binding to Sudlow II site; data for Sudlow I see Supporting Information Figure S3). Albumin digestion with Proteinase K was indistinguishable between the pristine and the glycosylated albumin (Figure 2C).…”

Section: Resultsmentioning

confidence: 99%

Per‐glycosylation of the Surface‐Accessible Lysines: One‐Pot Aqueous Route to Stabilized Proteins with Native Activity

et al. 2021

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Chemical glycosylation of proteins is a powerful tool applied widely in biomedicine and biotechnology. However, it is a challenging undertaking and typically relies on recombinant proteins and site-specific conjugations. The scope and utility of this nature-inspired methodology would be broadened tremendously by the advent of facile, scalable techniques in glycosylation, which are currently missing. In this work, we investigated a one-pot aqueous protocol to achieve indiscriminate, surface-wide glycosylation of the surface accessible amines (lysines and/or N-terminus). We reveal that this approach afforded minimal if any change in the protein activity and recognition events in biochemical and cell culture assays, but at the same time provided a significant benefit of stabilizing proteins against aggregation and fibrillation -as demonstrated on serum proteins (albumins and immunoglobulin G, IgG), an enzyme (uricase), and proteins involved in neurodegenerative disease (α-synuclein) and diabetes (insulin). Most importantly, this highly advantageous result was achieved via a one-pot aqueous protocol performed on native proteins, bypassing the use of complex chemical methodologies and recombinant proteins.

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Section: Resultsmentioning

confidence: 99%

Per‐glycosylation of the Surface‐Accessible Lysines: One‐Pot Aqueous Route to Stabilized Proteins with Native Activity

et al. 2021

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“…Albumin is a protein abundant in serum, while 20%-30% of them can cross the capillary endothelial barriers and enter the lymphatic system ( 40 ). More importantly, with a MW of 66 kDa, albumin exceeds the MW cut-off (45 kDa) that passes through the tight junctions of endothelial cells and the basement membranes of blood vessels ( 41 , 42 ).…”

Section: Discussionmentioning

confidence: 99%

“…In this study, we applied a streptococcus G protein-derived ABD peptide and hoped that it can facilitate the dLNs-targeting of VP1 vaccine by its noncovalent binding with the serum albumin. Albumin is a protein abundant in serum, while 20%-30% of them can cross the capillary endothelial barriers and enter the lymphatic system (40). More importantly, with a MW of 66 kDa, albumin exceeds the MW cut-off (45 kDa) that passes through the tight junctions of endothelial cells and the basement membranes of blood vessels (41,42).…”

Section: Discussionmentioning

confidence: 99%

An Albumin-Binding Domain Peptide Confers Enhanced Immunoprotection Against Viral Myocarditis by CVB3 VP1 Vaccine

2021

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Coxsackievirus B3 (CVB3)-induced viral myocarditis is a common clinical cardiovascular disease without effective available vaccine. In this study, we tried to potentiate the immunoprotection efficacy of our previous CVB3-specific VP1 protein vaccine by introducing a streptococcal protein G-derived, draining lymph nodes (dLNs)-targeting albumin-binding domain (ABD) peptide. We found that compared with the original VP1 vaccine, ABD-fused VP1 (ABD-VP1) vaccine gained the new ability to efficiently bind murine albumin both in vitro and in vivo, possessed a much longer serum half-life in serum and exhibited more abundance in the dLNs after immunization. Accordingly, ABD-VP1 immunization not only significantly facilitated the enrichment and maturation of dendritic cells (DCs), induced higher percentages of IFN-γ+ CD8+ cells in the dLNs, but also robustly promoted VP1-induced T cell proliferation and cytotoxic T lymphocyte (CTL) responses in the spleens. More importantly, ABD-VP1 also elicited higher percentages of protective CD44hi CD62Lhi memory T cells in dLNs and spleens. Consequently, obvious protective effect against viral myocarditis was conferred by ABD-VP1 vaccine compared to the VP1 vaccine, reflected by the less body weight loss, improved cardiac function, alleviated cardiac histomorphological changes and an increased 28-day survival rate. Our results indicated that the ABD might be a promising immune-enhancing regime for vaccine design and development.

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“…86 As such, albumin-bound cancer drugs accumulate in solid tumors and show an enhanced anti-tumor effect. [86][87][88][89] This is supported by studies demonstrating that albumin accumulation is caused by the so-called "enhanced permeability and retention effect" where higher permeability of blood capillaries increases accumulation in the tumor. Based on this, it may well be that ABD-fused IgA1 in complex with albumin could be taken up by tumors more efficiently that unfused IgA1.…”

Section: E1893888-6mentioning

confidence: 99%

Extended plasma half-life of albumin-binding domain fused human IgA upon pH-dependent albumin engagement of human FcRnin vitroandin vivo

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Meyer

et al. 2021

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Lymphatic targeting by albumin-hitchhiking: Applications and optimisation

Cited by 69 publications

References 154 publications

Per‐glycosylation of the Surface‐Accessible Lysines: One‐Pot Aqueous Route to Stabilized Proteins with Native Activity

Per‐glycosylation of the Surface‐Accessible Lysines: One‐Pot Aqueous Route to Stabilized Proteins with Native Activity

An Albumin-Binding Domain Peptide Confers Enhanced Immunoprotection Against Viral Myocarditis by CVB3 VP1 Vaccine

Extended plasma half-life of albumin-binding domain fused human IgA upon pH-dependent albumin engagement of human FcRnin vitroandin vivo

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