Conjugation of staphylokinase with the arabinogalactan-PEG conjugate: Study on the immunogenicity, in vitro bioactivity and pharmacokinetics

Qi, Fangbing; Qi, Jinming; Hu, Chunyang; Shen, Lijuan; Wang, Yu; Hu, Tao

doi:10.1016/j.ijbiomac.2019.03.046

Cited by 8 publications

(4 citation statements)

References 27 publications

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“…However, it has a short life-time in the blood, which limits the clinical application. Strategies based on the PEGylation (attachment of polyethylene glycol) may prolong the half-life time of staphylokinase, thereby improving its bioactivity in disease conditions ( 312 ).…”

Section: Other Pharmacological Approachesmentioning

confidence: 99%

Extracellular DNA Traps: Origin, Function and Implications for Anti-Cancer Therapies

et al. 2022

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Extracellular DNA may serve as marker in liquid biopsies to determine individual diagnosis and prognosis in cancer patients. Cell death or active release from various cell types, including immune cells can result in the release of DNA into the extracellular milieu. Neutrophils are important components of the innate immune system, controlling pathogens through phagocytosis and/or the release of neutrophil extracellular traps (NETs). NETs also promote tumor progression and metastasis, by modulating angiogenesis, anti-tumor immunity, blood clotting and inflammation and providing a supportive niche for metastasizing cancer cells. Besides neutrophils, other immune cells such as eosinophils, dendritic cells, monocytes/macrophages, mast cells, basophils and lymphocytes can also form extracellular traps (ETs) during cancer progression, indicating possible multiple origins of extracellular DNA in cancer. In this review, we summarize the pathomechanisms of ET formation generated by different cell types, and analyze these processes in the context of cancer. We also critically discuss potential ET-inhibiting agents, which may open new therapeutic strategies for cancer prevention and treatment.

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Section: Other Pharmacological Approachesmentioning

confidence: 99%

Extracellular DNA Traps: Origin, Function and Implications for Anti-Cancer Therapies

et al. 2022

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“…Qi et al utilized a low MW PEG (2 or 5 kDa) that lacked a methoxyl moiety as a linker to conjugate arabinogalactan (AG) to staphylokinase (SAK) [68] in order to enhance SAK efficacy through a reduction of immunogenicity, improved half-life and stabilized bioactivity. AG is a 38 kDa polysaccharide macromolecule that, when interfaced with SAK, significantly increases the molecular weight of the complex, allowing for avoidance of glomerular filtration.…”

Section: Effect Of An Encapsulated Drugmentioning

confidence: 99%

“…A low MW PEG that lacks methoxyl has been shown to additionally trigger a weak anti-PEG immune response and to decrease the steric shielding effect of AG. Subsequently, AG-PEG-SAK conjugation did not induce any AGor PEG-specific immune response, and it significantly enhanced the therapeutic efficacy of SAK [68]. Thus, cell membrane-camouflaged NPs could serve as an alternative to PEGylation without the undesirable generation of anti-PEG antibodies, with the modified NPs gaining additional functionality by harnessing the inherent properties of the incorporated membrane protein such as improved biocompatibility and cell contact.…”

Section: Effect Of An Encapsulated Drugmentioning

confidence: 99%

The Importance of Poly(ethylene glycol) Alternatives for Overcoming PEG Immunogenicity in Drug Delivery and Bioconjugation

et al. 2020

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Poly(ethylene glycol) (PEG) is widely used as a gold standard in bioconjugation and nanomedicine to prolong blood circulation time and improve drug efficacy. The conjugation of PEG to proteins, peptides, oligonucleotides (DNA, small interfering RNA (siRNA), microRNA (miRNA)) and nanoparticles is a well-established technique known as PEGylation, with PEGylated products have been using in clinics for the last few decades. However, it is increasingly recognized that treating patients with PEGylated drugs can lead to the formation of antibodies that specifically recognize and bind to PEG (i.e., anti-PEG antibodies). Anti-PEG antibodies are also found in patients who have never been treated with PEGylated drugs but have consumed products containing PEG. Consequently, treating patients who have acquired anti-PEG antibodies with PEGylated drugs results in accelerated blood clearance, low drug efficacy, hypersensitivity, and, in some cases, life-threatening side effects. In this succinct review, we collate recent literature to draw the attention of polymer chemists to the issue of PEG immunogenicity in drug delivery and bioconjugation, thereby highlighting the importance of developing alternative polymers to replace PEG. Several promising yet imperfect alternatives to PEG are also discussed. To achieve asatisfactory alternative, further joint efforts of polymer chemists and scientists in related fields are urgently needed to design, synthesize and evaluate new alternatives to PEG.

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“…The concentration of GPx1M or SS-mPEG-GPx1M in serum was assayed by a competitive inhibition ELISA kit. The pharmacokinetic data were calculated with PKSolver 2.0 software [43][44][45].…”

Section: Pharmacokinetics Analysis Of Ss-mpeg-gpx1mmentioning

confidence: 99%

PEGylation and antioxidant effects of a human glutathione peroxidase 1 mutant

Zhang

Wang

Guo

et al. 2022

Aging

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Human glutathione peroxidase1 (hGPx1) is a good antioxidant and potential drug, but the limited availability and poor stability of hGPx1 have affected its development and application. To solve this problem, we prepared a hGPx1 mutant (GPx1M) with high activity in an Escherichia coli BL21(DE3)cys auxotrophic strain using a single protein production (SPP) system. In this study, the GPx1M was conjugated with methoxypolyethylene glycol-succinimidyl succinate (SS-mPEG, M w = 5 kDa) chains to enhance its stability. SS-mPEG-GPx1M and GPx1M exhibited similar enzymatic activity and stability toward pH and temperature change, and in a few cases, SS-mPEG-GPx1M was discovered to widen the range of pH stability and increase the temperature stability. Lys 38 was confirmed as PEGylated site by liquid-mass spectrometry. H9c2 cardiomyoblast cells and Sprague-Dawley (SD) rats were used to evaluate the effects of GPx1M and SS-mPEG-GPx1M on preventing or alleviating adriamycin (ADR)-mediated cardiotoxicity, respectively. The results indicated that GPx1M and SS-mPEG-GPx1M had good antioxidant effects in vitro and in vivo , and the effect of SS-mPEG-GPx1M is more prominent than GPx1M in vivo . Thus, PEGylation might be a promising method for the application of GPx1M as an important antioxidant and potential drug.

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Conjugation of staphylokinase with the arabinogalactan-PEG conjugate: Study on the immunogenicity, in vitro bioactivity and pharmacokinetics

Cited by 8 publications

References 27 publications

Extracellular DNA Traps: Origin, Function and Implications for Anti-Cancer Therapies

Extracellular DNA Traps: Origin, Function and Implications for Anti-Cancer Therapies

The Importance of Poly(ethylene glycol) Alternatives for Overcoming PEG Immunogenicity in Drug Delivery and Bioconjugation

PEGylation and antioxidant effects of a human glutathione peroxidase 1 mutant

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