Leukemia Inhibitory Factor-Loaded Nanoparticles with Enhanced Cytokine Metabolic Stability and Anti-Inflammatory Activity

Davis, Stephanie M.; Reichel, Derek; Bae, Younsoo; Pennypacker, Keith R.

doi:10.1007/s11095-017-2282-4

Cited by 17 publications

(15 citation statements)

References 24 publications

(26 reference statements)

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“…Despite the lack of positive response to LIF, patients showed no side effects, confirming the promising use of LIF for systemic treatments. Moreover, a recent study designed and synthetised LIF-loaded and vectorised nanoparticles for the targeting of activated peripheral macrophages, which were able to decrease murine leukemic cell M1 proliferation [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Leukaemia Inhibitory Factor (LIF) Inhibits Cancer Stem Cells Tumorigenic Properties through Hippo Kinases Activation in Gastric Cancer

Seeneevassen

Giraud

Molina-Castro

et al. 2020

Cancers

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Cancer stem cells (CSCs) present chemo-resistance mechanisms contributing to tumour maintenance and recurrence, making their targeting of utmost importance in gastric cancer (GC) therapy. The Hippo pathway has been implicated in gastric CSC properties and was shown to be regulated by leukaemia inhibitory factor receptor (LIFR) and its ligand LIF in breast cancer. This study aimed to determine LIF’s effect on CSC properties in GC cell lines and patient-derived xenograft (PDX) cells, which remains unexplored. LIF’s treatment effect on CSC markers expression and tumoursphere formation was evaluated. The Hippo kinase inhibitor XMU-MP-1 and/or the JAK1 inhibitor Ruxolitinib were used to determine Hippo and canonical JAK/STAT pathway involvement in gastric CSCs’ response to LIF. Results indicate that LIF decreased tumorigenic and chemo-resistant CSCs, in both GC cell lines and PDX cells. In addition, LIF increased activation of LATS1/2 Hippo kinases, thereby decreasing downstream YAP/TAZ nuclear accumulation and TEAD transcriptional activity. LIF’s anti-CSC effect was reversed by XMU-MP-1 but not by Ruxolitinib treatment, highlighting the opposite effects of these two pathways downstream LIFR. In conclusion, LIF displays anti-CSC properties in GC, through Hippo kinases activation, and could in fine constitute a new CSCs-targeting strategy to help decrease relapse cases and bad prognosis in GC.

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Section: Discussionmentioning

confidence: 99%

Leukaemia Inhibitory Factor (LIF) Inhibits Cancer Stem Cells Tumorigenic Properties through Hippo Kinases Activation in Gastric Cancer

Seeneevassen

Giraud

Molina-Castro

et al. 2020

Cancers

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“…In another report, Stephanie et al successfully delivered Leukemia Inhibitory Factor (LIF) by fabricating poly(ethylene glycol)–poly(lactic acid) (PEG-PLA) polymer backbone polymeric nanoparticles (NanoLIF) and modified their surfaces with a CD-11b antibody (CD-11b-NanoLIF) to target peripheral-macrophages. The results indicated that the CD11-b-NanoLIF successfully targeted the activated peripheral-macrophages and significantly decreased inflammation by inhibiting M1-cell growth over 72 hrs as compared to the free LIF 176. In conclusion, polymeric nanoparticles either surface modified or naked could be an important strategy to treat AS and localized inflammatory disorders.…”

Section: Nanotechnology-based Treatment Approaches For Asmentioning

confidence: 88%

<p>Advances in nanomedicine for the treatment of ankylosing spondylitis</p>

Xi¹,

Jiang²,

Chaurasiya³

et al. 2019

IJN

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Ankylosing spondylitis (AS) is a complex disease characterized by inflammation and ankylosis primarily at the cartilage–bone interface. The disease is more common in young males and risk factors include both genetic and environmental. While the pathogenesis of AS is not completely understood, it is thought to be an immune-mediated disease involving inflammatory cellular infiltrates, and human leukocyte antigen-B27. Currently, there is no specific diagnostic technique available for this disease; therefore conventional diagnostic approaches such as clinical symptoms, laboratory tests and imaging techniques are used. There are various review papers that have been published on conventional treatment approaches, and in this review work, we focus on the more promising nanomedicine-based treatment modalities to move this field forward.

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“…The latter is one of the major reasons why the delivery of cytokines is yet to be fully explored. Regardless, nanoparticles remain the most used vehicle for this purpose and many types have been studied that include sources such as polymeric [32,33], chitosan [14], gold [34], silica [35], magnetic [36] to liposomal [37,38] nanoparticles (Table 1). The cytokines can be encapsulated, adsorbed or conjugated into the nanocarrier system, and the nanometric size of these delivery systems increases the absorption of the drug by the cells, when compared to larger particles.…”

Section: Nanoparticles As Cytokine Delivery Systemsmentioning

confidence: 99%

Nanotechnology Solutions for Controlled Cytokine Delivery: An Applied Perspective

et al. 2020

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Around 200 cytokines with roles in cell signaling have been identified and studied, with the vast majority belonging to the four-α-helix bundle family. These proteins exert their function by binding to specific receptors and are implicated in many diseases. The use of several cytokines as therapeutic targets has been approved by the FDA, however their rapid clearance in vivo still greatly limits their efficacy. Nano-based drug delivery systems have been widely applied in nanomedicine to develop safe, specific and controlled delivery techniques. Nevertheless, each nanomaterial has its own specifications and their suitability towards the biochemical and biophysical properties of the selected drug needs to be determined, weighing in the final choice of the ideal nano drug delivery system. Nanoparticles remain the most used vehicle for cytokine delivery, where polymeric carriers represent the vast majority of the studied systems. Liposomes and gold or silica nanoparticles are also explored and discussed in this review. Additionally, surface functionalization is of great importance to facilitate the attachment of a wide variety of molecules and modify features such as bioavailability. Since the monitoring of cytokine levels has an important role in early clinical diagnosis and for assessing therapeutic efficacy, nanotechnological advances are also valuable for nanosensor development.

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Leukemia Inhibitory Factor-Loaded Nanoparticles with Enhanced Cytokine Metabolic Stability and Anti-Inflammatory Activity

Abstract: NanoLIF and CD11b-NanoLIF preserved the metabolic stability and biological activity of LIF in vitro. These results are promising to improve the therapeutic potential of LIF in treating neurodegenerative and inflammatory diseases.

Cited by 17 publications

References 24 publications

Leukaemia Inhibitory Factor (LIF) Inhibits Cancer Stem Cells Tumorigenic Properties through Hippo Kinases Activation in Gastric Cancer

Leukaemia Inhibitory Factor (LIF) Inhibits Cancer Stem Cells Tumorigenic Properties through Hippo Kinases Activation in Gastric Cancer

<p>Advances in nanomedicine for the treatment of ankylosing spondylitis</p>

Nanotechnology Solutions for Controlled Cytokine Delivery: An Applied Perspective

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