Development of Autologous C5 Vaccine Nanoparticles to Reduce Intravascular Hemolysis <i>in Vivo</i>

Zhang, Lingjun; Qiao, Wen; Crooke, Stephen N.; Li, Yan; Abid, Areeba; Xu, Bin; Finn, M. G.; Lin, Feng

doi:10.1021/acschembio.6b00994

Cited by 17 publications

(17 citation statements)

References 44 publications

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“…Nanoparticle-based drug delivery approach has gained pace in recent years for both small molecules such as natural products as well as biomolecules such as peptides [112,114]. Nanoparticles can improve the effectiveness of natural compounds in disease treatment and prevention by increasing their bioavailability, including passing the BBB.…”

Section: Natural Product-based Amyloid Inhibitorsmentioning

confidence: 99%

Natural product-based amyloid inhibitors

Velander

Henderson

et al. 2017

Biochemical Pharmacology

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174

135

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Many chronic human diseases, including multiple neurodegenerative diseases, are associated with deleterious protein aggregates, also called protein amyloids. One common therapeutic strategy is to develop protein aggregation inhibitors that can slow down, prevent, or remodel toxic amyloids. Natural products are a major class of amyloid inhibitors, and several dozens of natural product-based amyloid inhibitors have been identified and characterized in recent years. These plant- or microorganism-extracted compounds have shown significant therapeutic potential from in vitro studies as well as in vivo animal tests. Despite the technical challenges of intrinsic disordered or partially unfolded amyloid proteins that are less amenable to characterizations by structural biology, a significant amount of research has been performed, yielding biochemical and pharmacological insights into how inhibitors function. This review aims to summarize recent progress in natural product-based amyloid inhibitors and to analyze their mechanisms of inhibition in vitro. Major classes of natural product inhibitors and how they were identified are described. Our analyses comprehensively address the molecular interactions between the inhibitors and relevant amyloidogenic proteins. These interactions are delineated at molecular and atomic levels, which include covalent, non-covalent, and metal-mediated mechanisms. In vivo animal studies and clinical trials have been summarized as an extension. To enhance natural product bioavailability in vivo, emerging work using nanocarriers for delivery has also been described. Finally, issues and challenges as well as future development of such inhibitors are envisioned.

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Section: Natural Product-based Amyloid Inhibitorsmentioning

confidence: 99%

Natural product-based amyloid inhibitors

Velander

Henderson

et al. 2017

Biochemical Pharmacology

Self Cite

174

135

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“…A peptide epitope (PADRE peptide) in the C5 vaccine is used to create a recombinant virus-like particles (VLPs). It showed a reduction in hemolytic activity and protect the mice from complement-mediated intravascular hemolysis [60]. Based on the study's result, it is showed that the recombinant VLPs could be used as an alternative or supplement for Eculizumab.…”

Section: Virus-like Particlementioning

confidence: 93%

“…Virus-like particles (VLPs) is one of the alternative types of nanoparticles delivery system [59]. A recent research has shown that the development of autologous C5 vaccine in nanoparticle form is able to elicit strong humoral responses [60]. A peptide epitope (PADRE peptide) in the C5 vaccine is used to create a recombinant virus-like particles (VLPs).…”

Section: Virus-like Particlementioning

confidence: 99%

New Generation Peptide-Based Vaccine Prototype

Özcan¹,

Karahan²,

Kumar³

et al. 2020

Current and Future Aspects of Nanomedicine

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Synthetic peptide-based vaccine prototypes are the future potential vaccination. Antigens, which belong to minimal microbial component and produce antibodies such as peptides and polysaccharides, can promote long-term protection against pathogens that can cause infectious diseases. Production of peptides becomes simple with solid phase peptide synthesis and microwave-assisted solid phase peptide synthesis using automatic synthesizers. The use of synthetic peptides was approved by the health authorities for vaccine design. Peptides are themselves very weak immunogens and need adjuvants to provide an effective autoimmune response. For this reason, peptide antigens are conjugated with biopolymers and loaded with nanoparticles. The toxicity of vaccine prototypes is evaluated in cell culture, and non-toxic prototypes are selected for vaccinating experimental animals. The most effective peptide-based vaccine prototype is determined as the one with the highest antibody level. The goal of this book chapter is to illustrate the use of peptides vaccine systems and present their opportunities with their future development.

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“…GOx is ∼160 kDa in size, consists of two dimers, two flavin adenine dinucleotide (FAD) and iron cofactors, and is heavily glycosylated, representing more complex multimeric and/or cofactor dependent proteins (Bankar et al, 2009). Lastly, the virus-like particle Qβ is a 30 nm multimeric protein assembly that has been extensively researched as a drug delivery, imaging, and immunotherapy platform (Pokorski et al, 2011; Spohn et al, 2008; Zhang et al, 2017). Our previous study utilized unmilled Qβ/PLGA HME formulations to serve as single-administration vaccine devices in vivo .…”

Section: Introductionmentioning

confidence: 99%

Milling solid proteins to enhance activity after melt-encapsulation

Lee

Maia

Pokorski

2017

International Journal of Pharmaceutics

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Polymeric systems for the immobilization and delivery of proteins have been extensively used for therapeutic and catalytic applications. While most devices have been created via solution based methods, hot melt extrusion (HME) has emerged as an alternative due to the high encapsulation efficiencies and solvent-free nature of the process. HME requires high temperatures and mechanical stresses that can result in protein aggregation and denaturation, but additives and chemical modifications have been explored to mitigate these effects. This study explores the use of solid-state ball milling to decrease protein particle size before encapsulation within poly (lactic-co-glycolic acid) (PLGA) via HME. The impact of milling on particle dispersion, retained enzymatic activity, secondary structure stability, and release was explored for lysozyme, glucose oxidase, and the virus-like particle derived from Qβ to fully understand the impact of milling on protein systems with different sizes and complexities. The results of this study describe the utility of milling to further increase the stability of protein/polymer systems prepared via HME.

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Development of Autologous C5 Vaccine Nanoparticles to Reduce Intravascular Hemolysis in Vivo

Cited by 17 publications

References 44 publications

Natural product-based amyloid inhibitors

Natural product-based amyloid inhibitors

New Generation Peptide-Based Vaccine Prototype

Milling solid proteins to enhance activity after melt-encapsulation

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