Polymeric mechanical amplifiers of immune cytokine-mediated apoptosis

Mitchell, Michael J.; Webster, Jamie; Chung, Amanda; Guimarães, Pedro Pires Goulart; Khan, Omar F.; Langer, Robert

doi:10.1038/ncomms14179

Cited by 28 publications

(23 citation statements)

References 56 publications

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“…Beyond gene delivery, polymeric NPs have also been utilized to sensitize tumor cells to TRAIL-mediated apoptosis in the presence of physiological forces. 108 Recent work from our lab has indicated that, in addition to chemical sensitizers, tumor cells become sensitized to TRAIL-mediated apoptosis in the presence of mechanical forces. 109 Mechanical force in the form of fluid shear stress, mimicking shear forces of those in the microvasculature in vivo , enhanced cancer cell TRAIL-mediated apoptosis in vitro compared to similar treatments under static conditions.…”

Section: Polymeric Nanoparticlesmentioning

confidence: 99%

Nanoparticles for Immune Cytokine TRAIL-Based Cancer Therapy

et al. 2018

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The immune cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has received significant attention as a cancer therapeutic due to its ability to selectively trigger cancer cell apoptosis without causing toxicity in vivo. While TRAIL has demonstrated significant promise in preclinical studies in mice as a cancer therapeutic, challenges including poor circulation half-life, inefficient delivery to target sites, and TRAIL resistance have hindered clinical translation. Recent advances in drug delivery, materials science, and nanotechnology are now being exploited to develop next-generation nanoparticle platforms to overcome barriers to TRAIL therapeutic delivery. Here, we review the design and implementation of nanoparticles to enhance TRAIL-based cancer therapy. The platforms we discuss are diverse in their approaches to the delivery problem and provide valuable insight into guiding the design of future nanoparticle-based TRAIL cancer therapeutics to potentially enable future translation into the clinic.

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Section: Polymeric Nanoparticlesmentioning

confidence: 99%

Nanoparticles for Immune Cytokine TRAIL-Based Cancer Therapy

et al. 2018

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“…Flow patterns on surfaces grafted with complex (say brush-like) structures have attracted much attention in the past decades due to their pivotal roles in both engineering 1 , like fabrication of microfluidic and nanofluidic devices 2 – 4 , and biomedical applications 5 , 6 (e.g. drug delivery 7 and organ culture 8 ). A commonly studied example of a brush-like soft matter surface is a polymer brush surface - a surface composed of polymer chains end-grafted onto a solid substrate, and the polymer chains can be stretched away from the surface when high-speed flow passes by 9 .…”

Section: Introductionmentioning

confidence: 99%

Regimes of Flow over Complex Structures of Endothelial Glycocalyx: A Molecular Dynamics Simulation Study

Feng

Ventikos

Luo

2018

Sci Rep

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Flow patterns on surfaces grafted with complex structures play a pivotal role in many engineering and biomedical applications. In this research, large-scale molecular dynamics (MD) simulations are conducted to study the flow over complex surface structures of an endothelial glycocalyx layer. A detailed structure of glycocalyx has been adopted and the flow/glycocalyx system comprises about 5,800,000 atoms. Four cases involving varying external forces and modified glycocalyx configurations are constructed to reveal intricate fluid behaviour. Flow profiles including temporal evolutions and spatial distributions of velocity are illustrated. Moreover, streamline length and vorticity distributions under the four scenarios are compared and discussed to elucidate the effects of external forces and glycocalyx configurations on flow patterns. Results show that sugar chain configurations affect streamline length distributions but their impact on vorticity distributions is statistically insignificant, whilst the influence of the external forces on both streamline length and vorticity distributions are trivial. Finally, a regime diagram for flow over complex surface structures is proposed to categorise flow patterns.

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“…Inspired by NK cell cytotoxic activity, liposomal systems functionalized with a cell adhesion receptor, E-selectin, and an immune cytokine, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL, also known as TNFSF10), that binds to death receptors on cancer cells to trigger apoptosis 107 have been developed to tether to immune cells in the circulation 105 . In mice, this approach improved the circulation half-life of TRAIL, killed tumour cells in the bloodstream and prevented the spontaneous metastasis of prostate cancer 108 .…”

Section: Drug Deliverymentioning

confidence: 99%

Engineering and physical sciences in oncology: challenges and opportunities

2017

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The principles of engineering and physics have been applied to oncology for nearly 50 years. Engineers and physical scientists have made contributions to all aspects of cancer biology, from quantitative understanding of tumour growth and progression to improved detection and treatment of cancer. Many early efforts focused on experimental and computational modelling of drug distribution, cell cycle kinetics and tumour growth dynamics. In the past decade, we have witnessed exponential growth at the interface of engineering, physics and oncology that has been fuelled by advances in fields including materials science, microfabrication, nanomedicine, microfluidics, imaging, and catalysed by new programmes at the National Institutes of Health (NIH), including the National Institute of Biomedical Imaging and Bioengineering (NIBIB), Physical Sciences in Oncology, and the National Cancer Institute (NCI) Alliance for Nanotechnology. Here, we review the advances made at the interface of engineering and physical sciences and oncology in four important areas: the physical microenvironment of the tumour and technological advances in drug delivery; cellular and molecular imaging; and microfluidics and microfabrication. We discussthe research advances, opportunities and challenges for integrating engineering and physical sciences with oncology to develop new methods to study, detect and treat cancer, and we also describe the future outlook for these emerging areas.

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Polymeric mechanical amplifiers of immune cytokine-mediated apoptosis

Cited by 28 publications

References 56 publications

Nanoparticles for Immune Cytokine TRAIL-Based Cancer Therapy

Nanoparticles for Immune Cytokine TRAIL-Based Cancer Therapy

Regimes of Flow over Complex Structures of Endothelial Glycocalyx: A Molecular Dynamics Simulation Study

Engineering and physical sciences in oncology: challenges and opportunities

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