Noncovalent PEGylation of l-Asparaginase Using PEGylated Polyelectrolyte

Kurinomaru, Takaaki; Shiraki, Kentaro

doi:10.1002/jps.24217

Cited by 35 publications

(33 citation statements)

References 33 publications

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“…Compared to the SS-βCD branches, PEGylated HER branches (SS-PEG-SS-HER) were long, bulky, hydrophilic, and flexible. In an aqueous environment, SS-PEG-SS-HER chains surround the small SS-βCD blocks on the surface of CNPs to improve the solubility of DL-CNPs and the protection of DOX in βCD from premature release in blood vessels [41][42][43]. When the DL-CNPs are delivered to the tumor, they are degraded in response to the high concentration of GSH, and DOX in βCD is released with exposure to an acidic environment.…”

Section: Loading and External Stimuli-trigger Release Of Doxmentioning

confidence: 99%

Dual pH- and GSH-Responsive Degradable PEGylated Graphene Quantum Dot-Based Nanoparticles for Enhanced HER2-Positive Breast Cancer Therapy

Van

Hong

et al. 2020

Nanomaterials

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Dual stimuli-responsive degradable carbon-based nanoparticles (DS-CNPs) conjugated with Herceptin (HER) and polyethylene glycol (PEG) have been designed for the treatment of HER2-positive breast cancer. Each component has been linked through disulfide linkages that are sensitive to glutathione in a cancer microenvironment. β-cyclodextrin (β-CD) on the surface of DS-CNPs formed an inclusion complex (DL-CNPs) with doxorubicin (DOX) at a high loading capacity of 5.3 ± 0.4%. In response to a high level of glutathione (GSH) and low pH in a tumor environment, DL-CNPs were rapidly degraded and released DOX in a controlled manner via disruption of host–guest inclusion. These novel DL-CNPs exhibited high cellular uptake with low toxicity, which induced the efficient inhibition of antitumor activity both in vitro and in vivo. Cell viability, confocal laser scanning microscopy, and animal studies indicate that DL-CNPs are a great platform with a synergistically enhanced antitumor effect from the dual delivery of HER and DOX in DL-CNPs.

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Section: Loading and External Stimuli-trigger Release Of Doxmentioning

confidence: 99%

Dual pH- and GSH-Responsive Degradable PEGylated Graphene Quantum Dot-Based Nanoparticles for Enhanced HER2-Positive Breast Cancer Therapy

Van

Hong

et al. 2020

Nanomaterials

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“…PEGylation, that is, the covalent attachment of poly(ethylene glycol) (PEG) chains to the surface of the protein , is the main posttransduction strategy to improve protein drugs, generating products known as biobetters. It may result in several benefits such as (1) protection of antigenic sites present on the protein surface; (2) prevention of in vivo recognition and degradation by proteolytic enzymes and endocytosis; (3) increase in the protein apparent size and hydrodynamic volume, reducing renal filtration and increasing in vivo half‐life; (4) increase in water solubility and a consequent decrease in aggregation due to steric repulsion among PEGylated surfaces; and (5) increase in thermal and mechanical stability .…”

Section: Introductionmentioning

confidence: 99%

Production of a novel N‐terminal PEGylated crisantaspase

Torres-Obreque

Meneguetti

Custodio

et al. 2019

Biotech and App Biochem

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Crisantaspase is an asparaginase enzyme produced by Erwinia chrysanthemi and used to treat acute lymphoblastic leukemia (ALL) in case of hypersensitivity to Escherichia coli L-asparaginase (ASNase). The main disadvantages of crisantaspase are the short half-life (10 H) and immunogenicity. In this sense, its PEGylated form (PEG-crisantaspase) could not only reduce immunogenicity but also improve plasma half-life. In this work, we developed a process to obtain a site-specific N-terminal PEGylated crisantaspase (PEG-crisantaspase). Crisantaspase was recombinantly expressed in E. coli BL21(DE3) strain cultivated in a shaker and in a 2-L bioreactor. Volumetric productivity in bioreactor increased 37% compared to shaker conditions (460 and 335 U L −1 H −1 , respectively). Crisantaspase was extracted by osmotic shock and purified by cation exchange chromatography, presenting specific activity of 694 U mg −1 , 21.7 purification fold, and yield of 69%. Purified crisantaspase was PEGylated with 10 kDa methoxy polyethylene glycol-N-hydroxysuccinimidyl (mPEG-NHS) at different pH values (6.5-9.0). The highest N-terminal pegylation yield (50%) was at pH 7.5 with the lowest poly-PEGylation ratio (7%). PEG-crisantaspase was purified by size exclusion chromatography and presented a K M value three times higher than crisantaspase (150 and 48.5 µM, respectively). Nonetheless, PEG-crisantaspase was found to be more stable at high temperatures and over longer periods of time. In 2 weeks, crisantaspase lost 93% of its specific activity, whereas PEG-crisantaspase was stable for 20 days. Therefore, the novel PEG-crisantaspase enzyme represents a promising biobetter alternative for the treatment of ALL.

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“…The salt responsibility of PPC is generally independent of the state of the PPC. The release of protein molecules from a PPC is influenced not only by the incremental increase in ionic strength but also by the addition of other electrolyte, including polyelectrolytes and proteins, and hence are used in several applications, such as purification [36,[41][42][43][44][45], enzyme switch [24,[30][31][32], biosensors [46][47][48], and drug delivery systems [25,49,50]. 6 …”

Section: Formation Of Aggregative Ppcmentioning

confidence: 99%

“…Polyelectrolytes, charged linear polymers, have great potential as protein stabilizers [22][23][24][25][26][27][28][29] and functionalizing agents [30][31][32][33]. As described below, polyelectrolytes bind to complementary charged proteins, resulting in the formation of a protein-polyelectrolyte complex (PPC).…”

Section: Introductionmentioning

confidence: 99%