The Advances of Neutrophil-Derived Effective Drug Delivery Systems: A Key Review of Managing Tumors and Inflammation

Wang, Huaiji; Zang, Jie; Zhao, Zihan; Zhang, Qin; Chen, Shunjie

doi:10.2147/ijn.s328705

Cited by 41 publications

(25 citation statements)

References 90 publications

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“…Treated animals showed improved osteogenesis and vasculogenesis, resulting in skull healing 102 . Others have shown similar successful delivery of mRNAs or protein cargos using MSCs, neutrophils, monocytes and erythrocytes [98][99][100][101]103 .…”

Section: Cell-based Packagingmentioning

confidence: 94%

“…This approach could also be combined with existing cellular therapies to accentuate desired therapeutic or kinetic effects. However, cell-based delivery of mRNA therapeutics may be limited by the same caveats that apply to cell therapies in general, such as donor haplotype compatibility, homogeneous production, cumbersome quality control and a restricted intracellular delivery capacity 103 (Fig. 3c).…”

Section: Cell-based Packagingmentioning

confidence: 99%

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Unlocking the promise of mRNA therapeutics

et al. 2022

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z and enhanced catalysis to the ribosomal complex [32][33][34][35][36] . Optimization of the poly(A) tail length (100-300 nucleotides) has proven critical in balancing the synthetic capability of a given mRNA 34,36 . Similarly, improved 5′ cap analogs not only increase translational capacity but also enhance capping efficiency, from 70% to 95%, greatly improving the in vitro transcription process 32,37 . The composition of the 3′ and 5′ UTRs can also be customized for the target cell of interest, increasing the efficiency and tissue specificity of translation 35,38,39 .At present, most mRNA products contain a synthetic UTR sequence from α-globin or β-globin [38][39][40] , but UTR optimization can further improve protein expression by a few fold 41,42 . Careful screening and customization to the target of interest could conceivably offer a wide range of improvements in future UTR sequences, allowing each mRNA to be tailored to the targeted cell and disease-induced microenvironment to maximize protein synthesis per mRNA transcript [41][42][43][44] .Perhaps the most critical advances in mRNA vaccines and therapeutics lie in the discovery that the inclusion of chemically modified nucleosides, particularly in uridine moieties, can markedly increase protein expression after in vitro or in vivo transfection. The chemical modifications of most new RNA formulations to date have been central in intellectual property claims 45,46 . Thus far, over 130 different naturally occurring chemical modifications of RNA have been reported 47,48 . The interest in methylpseudouridine and other modified nucleosides centers on their capacity to greatly reduce (up to 100-fold) detection by the Toll-like receptors of the innate immune system, resulting in an increase in protein expression in vivo compared to unmodified mRNA 40,[49][50][51][52][53] . Combinations of different types of chemical modifications, carriers, for the treatment of chronic conditions. The fifth section provides a comprehensive table and summary of current clinical trends in mRNA therapeutics. Finally, the sixth section considers the scope of mRNA therapeutics and guiding principles for near-term and longer-term clinical development of this novel therapeutic modality.

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Section: Cell-based Packagingmentioning

confidence: 94%

Section: Cell-based Packagingmentioning

confidence: 99%

Unlocking the promise of mRNA therapeutics

et al. 2022

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“…Neutrophils hold natural potential to traverse the blood-brain barrier (335) and rapidly penetrate into the glioma tumor site (336). Therefore, in recent years, neutrophil-derived EVs have been studied as drug delivery vehicles in tumor therapy (337). Previously, Wang et al have shown that neutrophil-exosomeloaded drugs effectively penetrate the blood-brain barrier and migrate into brain.…”

Section: Potential Role Of Neutrophil-derived Extracellular Vesicles ...mentioning

confidence: 99%

Neutrophils: Musketeers against immunotherapy

et al. 2022

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Neutrophils, the most copious leukocytes in human blood, play a critical role in tumorigenesis, cancer progression, and immune suppression. Recently, neutrophils have attracted the attention of researchers, immunologists, and oncologists because of their potential role in orchestrating immune evasion in human diseases including cancer, which has led to a hot debate redefining the contribution of neutrophils in tumor progression and immunity. To make this debate fruitful, this review seeks to provide a recent update about the contribution of neutrophils in immune suppression and tumor progression. Here, we first described the molecular pathways through which neutrophils aid in cancer progression and orchestrate immune suppression/evasion. Later, we summarized the underlying molecular mechanisms of neutrophil-mediated therapy resistance and highlighted various approaches through which neutrophil antagonism may heighten the efficacy of the immune checkpoint blockade therapy. Finally, we have highlighted several unsolved questions and hope that answering these questions will provide a new avenue toward immunotherapy revolution.

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“…Under the guidance of cytokines and chemokines, PMNs migrate and infiltrate into the site of inflammation within a few minutes [ 87 , 137 ]. Like other immune cells, the extravasation of neutrophils is facilitated by multiple interactions with the endothelium, such as the interaction between intercellular adhesion molecule 1 (ICAM-1) upregulated on the inflamed endothelium and the integrin β2 expressed on neutrophils [ 138 ]. To take advantage of this interaction to actively deliver the anti-inflammatory drug TPCA-1 (5- p -Fluorophenyl-2-ureido-thiophene-3-carboxamide) to inflamed endothelial cells, Gao et al [ 122 ] used neutrophils nanovesicles obtained by nitrogen cavitation, ultracentrifugation, and extrusion of HL 60 cells, as a delivery system.…”

Section: Implications Of Inflammation In Covid-19 Therapies and Drug ...mentioning

confidence: 99%