Intracellular drug delivery: Potential usefulness of engineered Shiga toxin subunit B for targeted cancer therapy

Luginbuehl, Vera; Meier, Nicolas; Kovar, Karin; Rohrer, Jack

doi:10.1016/j.biotechadv.2018.02.005

Cited by 40 publications

(38 citation statements)

References 92 publications

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“…Alternative to inhibiting retrograde trafficking, current research has demonstrated an effort to capture the retrotranslocation mechanisms of toxins and repurpose them for drug delivery. Using the non-toxic subunit B of Shiga-like toxin, various attempts at conjugating therapeutics, incorporating nanoparticles, or developing fusion proteins have been attempted (reviewed in Luginbuehl et al [134] ).…”

Section: Therapeutic Targeting Of Retrotranslocationmentioning

confidence: 99%

Wrong place at the wrong time: how retrograde trafficking drives cancer metastasis through receptor mislocalization

Maisel¹,

Schroeder²

2019

JCMT

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Retrograde trafficking is a well-regulated, multi-component pathway that can result in endosomal trafficking to the trans-Golgi network, the perinuclear space, or the nucleus. Either clathrin or the retromer complex can travel with proteins endocytosed from the plasma membrane, guided by Rabs (including 5, 6, 7, 9, 22A), interacting with a host of sorting nexin proteins, and fusing with Golgi-specific anchors to allow transport of activated receptor tyrosine kinases to a potential end within the nucleus. Amplification in these constituents is common in cancer, leading to increased retrotranslocation and a reduction in degradation of receptor tyrosine kinases, an event highly associated with cancer metastasis. Here, we review the role of retrograde trafficking in altering transmembrane receptor localization and activity and the relationship to metastasis, focusing on all four members of the ErbB family, with comparison to other receptor tyrosine kinases including the insulin receptor and fibroblast growth factor receptor, as well as other transmembrane proteins dysregulated in metastasis. By examining how these receptors are being alternatively trafficked and the cancer-associated events resulting from this process, we hope to identify novel therapeutic targets.

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Section: Therapeutic Targeting Of Retrotranslocationmentioning

confidence: 99%

Wrong place at the wrong time: how retrograde trafficking drives cancer metastasis through receptor mislocalization

Maisel¹,

Schroeder²

2019

JCMT

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“…In some cases, parts of these toxins responsible for cytoplasm delivery are precisely mapped and can be used for improvement of the endosome escape efficacy of other therapeutic agents. For example, StxB can be used as a tool for cell delivery of various cargo through endocytosis and retrograde traffic [ 64 ]. In turn, the translocation domain of PE was used to enhance cytoplasm delivery of hybrid agents based on Shiga-like toxin 2; the resulting fusion protein N8A-TDP-Stx2B inhibited the growth of hepatocellular carcinoma cells HepG2 with a half-maximal inhibitory concentration (IC 50 ) of approximately 1 nM and was further tested in mouse xenograft model [ 65 ].…”

Section: Soluble Targeted Toxinsmentioning

confidence: 99%

Natural and Designed Toxins for Precise Therapy: Modern Approaches in Experimental Oncology

Shilova

Шрамова

Прошкина

et al. 2021

IJMS

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Cancer cells frequently overexpress specific surface receptors providing tumor growth and survival which can be used for precise therapy. Targeting cancer cell receptors with protein toxins is an attractive approach widely used in contemporary experimental oncology and preclinical studies. Methods of targeted delivery of toxins to cancer cells, different drug carriers based on nanosized materials (liposomes, nanoparticles, polymers), the most promising designed light-activated toxins, as well as mechanisms of the cytotoxic action of the main natural toxins used in modern experimental oncology, are discussed in this review. The prospects of the combined therapy of tumors based on multimodal nanostructures are also discussed.

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“…Since the underpinning of all toxicology is understanding cellular function down to the molecular level, super-resolution, especially live-cell modalities, will play a crucial role. Nanocrystals, which can function as both a small-molecule delivery system and an imaging target, are yet to be fully explored (Luginbuehl, Meier, Kovar, & Rohrer, 2018). These crystals hold promise of a complete paradigm shift both in drug delivery and imaging.…”

Section: The Future In a Nanoscopy Worldmentioning

confidence: 99%

Toxicology in the Super‐Resolution Era

Cole

2019

CP Toxicology

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Light microscopy has played a central role in science for the past couple of hundred years and will continue to do so. Multiple super‐resolution microscopy techniques have been in the headlines for smashing what for more than 100+ years was believed to be the limits of optical microscopy. This resolution improvement enables the visualization of molecular structures and processes on the nano scale. While certain scientific questions in toxicology can benefit from modalities within the super‐resolution suite, due diligence is required for efficiency and to achieve optimal results. For a given hypothesis being tested, there are biophysical issues that need to be considered before heading down the super‐resolution road. All commercially available super‐resolution modalities, along with cautions and tips, will be discussed. © 2019 by John Wiley & Sons, Inc.

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Intracellular drug delivery: Potential usefulness of engineered Shiga toxin subunit B for targeted cancer therapy

Cited by 40 publications

References 92 publications

Wrong place at the wrong time: how retrograde trafficking drives cancer metastasis through receptor mislocalization

Wrong place at the wrong time: how retrograde trafficking drives cancer metastasis through receptor mislocalization

Natural and Designed Toxins for Precise Therapy: Modern Approaches in Experimental Oncology

Toxicology in the Super‐Resolution Era

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