Platelet-Membrane-Coated Nanoparticles Enable Vascular Disrupting Agent Combining Anti-Angiogenic Drug for Improved Tumor Vessel Impairment

Nano Letters ◽  
2021 ◽  
Vol 21 (6) ◽  
pp. 2588-2595
Author(s):  
Bozhao Li ◽  
Tianjiao Chu ◽  
Jingyan Wei ◽  
Yinlong Zhang ◽  
Feilong Qi ◽  
...  
Keyword(s):  
Platelet Membrane ◽  
Tumor Vessel ◽  
Vascular Disrupting Agent ◽  
Coated Nanoparticles ◽  
Vascular Disrupting

Platelet membrane-coated nanoparticles target sclerotic aortic valves in ApoE−/− mice by multiple binding mechanisms under pathological shear stress

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Yang ◽  
Y Song ◽  
Z Huang ◽  
J Qian ◽  
Z Pang ◽  
...  
Keyword(s):  
Shear Stress ◽  
Aortic Valve ◽  
Aortic Valve Disease ◽  
Binding Capacity ◽  
Platelet Membrane ◽  
Valve Disease ◽  
Funding Source ◽  
Aortic Valves ◽  
Coated Nanoparticles

Abstract Background Aortic valve disease is the most common valvular heart disease leading to valve replacement. The efficacy of pharmacological therapy for aortic valve disease is limited by the high mechanical stress at the aortic valves impairing the binding rate. We aimed to identify nanoparticle coating with entire platelet membranes to fully mimic their inherent multiple adhesion mechanisms and target the sclerotic aortic valve of apolipoprotein E-deficient (ApoE−/−) mice based on their multiple sites binding capacity under high shear stress. Methods Considering the potent interaction of platelet membrane glycoproteins with components present in sclerotic aortic valves, platelet membrane-coated nanoparticles (PNPs) were synthetized and the binding capacity under high shear stress was evaluated in vitro and in vivo. Results Compared with PNPs bound intensity in the static station, 161%, 59%, and 39% of attached PNPs remained adherent on VWF-, collagen-, and fibrin-coated surfaces under shear stress of 25dyn/cm2 respectively. PNPs demonstrated effectively adhering to von Willebrand factor, collagen and fibrin under shear stresses in vitro. In an aortic valve disease model established in ApoE−/− mice, PNPs group exhibited significant increase of accumulation in the aortic valves compared with PBS and control NP group. PNPs displayed high degrees of proximity or co-localization with vWF, collagen and fibrin, which exhibited good targeting to sclerotic aortic valves by mimicking platelet multiple adhesive mechanisms. Conclusion PNPs could provide a promising platform for the molecular diagnosis and targeting treatment of aortic valve disease. Targeting combination Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China

The Novel Vascular Disrupting Agent ANG501 Induces Cell Cycle Arrest and Enhances Endothelial Cell Sensitivity to Radiation

2009 ◽  
Vol 2 ◽  
pp. CGM.S2596 ◽  
Author(s):  
Shona T. Dougherty ◽  
Sean E. Walker ◽  
Peter D. Davis ◽  
Graeme J. Dougherty
Keyword(s):  
Cell Cycle ◽  
Endothelial Cells ◽  
Normal Cell ◽  
Cell Cycle Progression ◽  
Stress Proteins ◽  
Vascular Disrupting Agent ◽  
Heat Shock Stress ◽  
Cell Cycling ◽  
Vascular Disrupting

The efficacy of approaches in which vascular disrupting agents (VDA) are used in combination with conventional chemotherapy and/or radiation therapy in the treatment of cancer might be improved if there were a better understanding of the cellular and molecular changes induced in normal and malignant cells as a result of VD A exposure. Toward this goal, murine endothelial cells were treated in vitro with ANG501, a novel stilbene VDA developed in our laboratory, and alterations in gene expression determined by genome-wide microarray analysis and subsequently confirmed by Western blot analysis. Among the genes that were shown to be induced upon brief exposure to non-cytotoxic doses of ANG501 were several involved in the control of cell cycle progression and apoptosis, including p21Wafl and the heat shock/stress proteins hsp25, hsp70 and anti-B-crystallin. Reflecting such induction, functional studies confirmed that normal cell cycling is temporarily inhibited following treatment with ANG501 such that the majority of cells accumulate at the radiation-sensitive G2/M phase of the cell cycle at 6 hr. The effects were transient and by 24 hr normal cell cycling had largely resumed. Combination experiments confirmed that endothelial cells treated 6 hr previously with ANG501 were more readily killed by radiation. Importantly, significant effects were evident at clinically relevant radiation doses. Taken together these findings emphasize the need to consider the radiosensitizing activity of VD As when developing therapies in which these promising compounds are used in combination with radiation.

Combretastatin A4 phosphate: a novel vascular disrupting agent

2010 ◽  
Vol 6 (8) ◽  
pp. 1219-1228 ◽  
Author(s):  
Govardhanan Nagaiah ◽  
Scot C Remick
Keyword(s):  
Vascular Disrupting Agent ◽  
Combretastatin A4 ◽  
Vascular Disrupting

scholarly journals Phase I trial of CYT997, a novel cytotoxic and vascular-disrupting agent

2010 ◽  
Vol 103 (5) ◽  
pp. 597-606 ◽  
Author(s):  
J D Lickliter ◽  
A B Francesconi ◽  
G Smith ◽  
M Burge ◽  
A Coulthard ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Trial ◽  
Vascular Disrupting Agent ◽  
Vascular Disrupting

scholarly journals The protective role of sphingosine-1-phosphate against the action of the vascular disrupting agent combretastatin A-4 3-O-phosphate

Oncotarget ◽  
2017 ◽  
Vol 8 (56) ◽  
pp. 95648-95661 ◽  
Author(s):  
Joanna Shepherd ◽  
Matthew Fisher ◽  
Abigail Welford ◽  
Donald M. McDonald ◽  
Chryso Kanthou ◽  
...  
Keyword(s):  
Protective Role ◽  
Vascular Disrupting Agent ◽  
Sphingosine 1 Phosphate ◽  
Vascular Disrupting

scholarly journals Intra-individual comparison of therapeutic responses to vascular disrupting agent CA4P between rodent primary and secondary liver cancers

2018 ◽  
Vol 24 (25) ◽  
pp. 2710-2721 ◽  
Author(s):  
Ye-Wei Liu ◽  
Frederik De Keyzer ◽  
Yuan-Bo Feng ◽  
Feng Chen ◽  
Shao-Li Song ◽  
...  
Keyword(s):  
Vascular Disrupting Agent ◽  
Individual Comparison ◽  
Liver Cancers ◽  
Therapeutic Responses ◽  
Vascular Disrupting

scholarly journals Phase I Safety, Pharmacokinetic and Pharmacodynamic Evaluation of the Vascular Disrupting Agent Ombrabulin (AVE8062) in Patients with Advanced Solid Tumors

2013 ◽  
Vol 19 (17) ◽  
pp. 4832-4842 ◽  
Author(s):  
Cristiana Sessa ◽  
Patricia Lorusso ◽  
Anthony Tolcher ◽  
Françoise Farace ◽  
Nathalie Lassau ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Advanced Solid Tumors ◽  
Vascular Disrupting Agent ◽  
Vascular Disrupting

scholarly journals Drug Targeting via Platelet Membrane–Coated Nanoparticles

2020 ◽  
Vol 1 (1) ◽  
pp. 2000018
Author(s):  
Shuyan Wang ◽  
Yaou Duan ◽  
Qiangzhe Zhang ◽  
Anvita Komarla ◽  
Hua Gong ◽  
...  
Keyword(s):  
Drug Targeting ◽  
Platelet Membrane ◽  
Coated Nanoparticles
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