Normalization of Tumour Blood Vessels Improves the Delivery of Nanomedicines in a Size-Dependent Manner

Abstract The mitotic spindle robustly scales with cell size in a plethora of different organisms. During development and throughout evolution, the spindle adjusts to cell size in metazoans and yeast in order to ensure faithful chromosome separation. Spindle adjustment to cell size occurs by the scaling of spindle length, spindle shape and the velocity of spindle assembly and elongation. Different mechanisms, depending on spindle structure and organism, account for these scaling relationships. The limited availability of critical spindle components, protein gradients, sequestration of spindle components, or post-translational modification and differential expression levels have been implicated in the regulation of spindle length and the spindle assembly/elongation velocity in a cell size-dependent manner. In this review, we will discuss the phenomenon and mechanisms of spindle length, spindle shape and spindle elongation velocity scaling with cell size.

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Faculty Opinions recommendation of Vascular bursts enhance permeability of tumour blood vessels and improve nanoparticle delivery.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726148599.793531613 ◽

2017 ◽

Author(s):

Xing-Jie Liang

Keyword(s):

Blood Vessels ◽

Nanoparticle Delivery ◽

Tumour Blood

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Ultrasound-stimulated microbubble enhancement of radiation response

Biological Chemistry ◽

10.1515/hsz-2014-0297 ◽

2015 ◽

Vol 396 (6-7) ◽

pp. 645-657 ◽

Cited By ~ 6

Author(s):

Gregory J. Czarnota

Keyword(s):

Blood Vessels ◽

Treatment Effectiveness ◽

Cancer Therapies ◽

Vascular Effect ◽

Ultrasonic Fields ◽

Normal Tissue Toxicity ◽

Tumour Vasculature ◽

Tumour Location ◽

Dependent Pathway ◽

Tumour Blood

Abstract Cancer therapies result in the killing of cancer cells but remain largely ineffective, with most patients dying of their disease. The methodology described here is a new image-guided cancer treatment under development that relies on physical methods to alter tumour biology. It enhances tumour responses to radiation significantly by synergistically destroying tumour blood vessels using microbubbles. It achieves tumour specificity by confining the ultrasonic fields that stimulate microbubbles to tumour location only. By perturbing tumour vasculature and activating specific genetic pathways in endothelial cells, the technique has been demonstrated to sensitise the targeted tissues to subsequent therapeutic application of radiation, resulting in significantly enhanced cell killing through a ceramide-dependent pathway initiated at the cell membrane. The treatment reviewed here destroys blood vessels, significantly enhancing the anti-vascular effect of radiation and improving tumour cure. The significant enhancement of localised tumour cell kill observed with this method means that radiation-based treatments can be potentially made more potent and lower doses of radiation utilised. The technique has the potential to have a profound impact on the practice of radiation oncology by offering a novel and safe means of reducing normal tissue toxicity while at the same time significantly increasing treatment effectiveness.

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Kisspeptin-10 Inhibits Angiogenesis in Human Placental Vessels ex Vivo and Endothelial Cells in Vitro

Endocrinology ◽

10.1210/en.2010-0565 ◽

2010 ◽

Vol 151 (12) ◽

pp. 5927-5934 ◽

Cited By ~ 32

Author(s):

Thayalini Ramaesh ◽

James J. Logie ◽

Antonia K. Roseweir ◽

Robert P. Millar ◽

Brian R. Walker ◽

...

Keyword(s):

Endothelial Cells ◽

Blood Vessels ◽

Ex Vivo ◽

Umbilical Vein ◽

Biologically Active ◽

Trophoblast Invasion ◽

In Vitro Assays ◽

Dependent Manner ◽

Inhibition Of Proliferation

Recent studies suggest that kisspeptin (a neuropeptide central to the regulation of gonadotrophin secretion) has diverse roles in human physiology, including a putative role in implantation and placental function. Kisspeptin and its receptor are present in human blood vessels, where they mediate vasoconstriction, and kisspeptin is known to inhibit tumor metastasis and trophoblast invasion, both processes involving angiogenesis. We hypothesized that kisspeptin contributes to the regulation of angiogenesis in the reproductive system. The presence of the kisspeptin receptor was confirmed in human placental blood vessels and human umbilical vein endothelial cells (HUVEC) using immunochemistry. The ability of kisspeptin-10 (KP-10) (a shorter biologically active processed peptide) to inhibit angiogenesis was tested in explanted human placental arteries and HUVEC using complementary ex vivo and in vitro assays. KP-10 inhibited new vessel sprouting from placental arteries embedded in Matrigel and tube-like structure formation by HUVEC, in a concentration-dependent manner. KP-10 had no effect on HUVEC viability or apoptosis but induced concentration-dependent inhibition of proliferation and migration. In conclusion, KP-10 has antiangiogenic effects and, given its high expression in the placenta, may contribute to the regulation of angiogenesis in this tissue.

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Correction to “Polystyrene Nanoparticles Reduced ROS and Inhibited Ferroptosis by Triggering Lysosome Stress and TFEB Nucleus Translocation in a Size-Dependent Manner”

Nano Letters ◽

10.1021/acs.nanolett.9b04770 ◽

2019 ◽

Vol 19 (12) ◽

pp. 9170-9170

Author(s):

Lin Li ◽

Shili Sun ◽

Lingli Tan ◽

Yuanfang Wang ◽

Luyao Wang ◽

...

Keyword(s):

Dependent Manner ◽

Polystyrene Nanoparticles ◽

Size Dependent

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Pesticide Encapsulation at the Nanoscale Drives Changes to the Hydrophobic Partitioning and Toxicity of an Active Ingredient

Nanomaterials ◽

10.3390/nano9010081 ◽

2019 ◽

Vol 9 (1) ◽

pp. 81 ◽

Cited By ~ 13

Author(s):

Matthew Slattery ◽

Bryan Harper ◽

Stacey Harper

Keyword(s):

Active Ingredient ◽

Large Fraction ◽

Ceriodaphnia Dubia ◽

Time Dependent ◽

Hydrodynamic Diameter ◽

Dependent Manner ◽

Size Dependent ◽

Pesticide Formulations ◽

Dependent Inhibition ◽

Time Dependent Inhibition

Given the costs associated with designing novel active ingredients, new formulations focus on the use of other ingredients to modify existing formulations. Nanosized encapsulated pesticides offer a variety of enhanced features including controlled release and improved efficacy. Despite the presence of nanosized capsules in current-use pesticide formulations, the analytical and toxicological implications of encapsulation are uncertain. To explore this issue quantitatively, we fractionated the capsules of a commercially available encapsulated insecticide formulation (γ-cyhalothrin active ingredient) into two size ranges: a large fraction (LF), with an average hydrodynamic diameter (HDD) of 758 nm, and a small fraction (SF), with an average HDD of 449 nm. We developed a novel extraction method demonstrating a time-dependent inhibition of γ-cyhalothrin from capsules for up to 48 h. An acute immobilization test with a freshwater macroinvertebrate (Ceriodaphnia dubia) revealed that the SF was significantly more toxic than both the LF and the free γ-cyhalothrin treatment (EC50 = 0.18 µg/L, 0.57 µg/L, and 0.65 µg/L, respectively). These findings highlight that encapsulation of γ-cyhalothrin mitigates hydrophobic partitioning in a time-dependent manner and influences toxicity in a size-dependent manner. Recognizing the analytical and toxicological nuances of various nanosized capsules can contribute to innovation in pesticide formulations and may lead to more comprehensive pesticide regulation.

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