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Codelivery in Nanoparticle-based siRNA for Cancer Therapy
Published in Loutfy H. Madkour, Nanoparticle-Based Drug Delivery in Cancer Treatment, 2022
Another strategy to reduce cytotoxicity of high molecular weight PEI is by grafting stearic acid (SA) to PEI through carbodiimide conjugation using 1-ethyl-3-(3-dimethylamino-propyl) carbodiimide (EDC) reaction [132]. PEI-SA micelles were formed using the oil in water (o/w) solvent evaporation method, obtaining small (≈51 nm) and cationic (≈64 mV) micelles. These micelles contain both a hydrophobic core that can encapsulate a hydrophobic drug and a hydrophilic cationic shell capable of complexing siRNA. DOX was encapsulated into the micelles by mild agitation. siRNA against the vascular endothelial growth factor (VEGF) was complexed onto the nanoparticle surface. VEGF is a growth factor over secreted by tumors to force the formation of new blood vessels by stimulating the growth and division of endothelial cells to provide oxygen-rich blood to tumor cells. This process is known as angiogenesis, and it has been proven to be necessary for the tumor to survive. By blocking the formation of new blood vessels irrigating the tumor with oxygen, tumor growth can be stopped. PEI-SA/DOX reduced the volume of the tumor down to 13% relative to the control. When using PEI-SA/DOX/viVEGF, the tumor was reduced down to 56.7%.
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Published in Valerio Voliani, Nanomaterials and Neoplasms, 2021
Eun-Kyung Lim, Taekhoon Kim, Soonmyung Paik, Seungjoo Haam, Yong-Min Huh, Kwangyeol Lee
VEGF is secreted from growing tumors to stimulate angiogenesis. Blockage of VEGF can be accomplished via neutralization of VEGF ligands or VEGF receptors using specific antibodies or via inhibition of VEGF activation and signaling using specific kinase inhibitors. Bevacizumab (Avastin), an angiogenesis inhibitor, is widely used to treat various cancers, including colorectal, lung, breast, and kidney cancers, as well as glioblastomas [214, 216, 401, 402].
Nanomedicine for the Treatment of Ocular Diseases
Published in Sarwar Beg, Mahfoozur Rahman, Md. Abul Barkat, Farhan J. Ahmad, Nanomedicine for the Treatment of Disease, 2019
Priyanka Prabhu, Saritha Shetty
Globally, numerous research efforts are directed towards enhancement of quality of life for people with diabetes. Diabetic retinopathy remains a major concern contributing to blindness. Increased VEGF signaling is also present in diabetic retinopathy. Hindering VEGF mediated angiogenesis can improve vision in diabetic retinopathy patients. Upregulation of human antigen R (HuR) protein in rats with diabetic retinopathy has been reported. Amodio et al. fabricated solid lipid nanoparticles and liposomes loaded with siRNA for HuR silencing. HuRsiRNA was bound to cationic vesicles made of ([2,3-dioleoxypropyl] N,N,trimethylamoniomethylphosphate) (DOTAP). Intraocular injection of liposomes and SLN drastically decreased retinal HuR and VEGF protein levels in diabetic rats (Amodio et al., 2016).
Diabetic retinopathy progression associated with haplotypes of two VEGFA SNPs rs2010963 and rs699947
Published in Egyptian Journal of Basic and Applied Sciences, 2023
Haider Ali Alnaji, Rabab Omran, Aizhar H. Hasan, Mohammed Qasim Al Nuwaini
as rs2010963 have been strongly linked with Recent meta-analysis findings indicated that rs2010963 was associated with PDR in the overall population VEGF protein in the blood [25]. The VEGF protein is a potent angiogenic agent in various diseases. It has been established that elevated serum and vitreous levels of VEGF in the presence of retinopathy are closely associated with proliferative diabetic retinopathy [26]. A study from Egypt explored the association between rs699947 SNP and the susceptibility of DR, and it found no significant association between them. This result is consistent with our findings [27]. Different studies also revealed no association between the presence of rs699947 SNP and the risk of DR [28]. In a previous meta-analysis, the rs699947 in Asian individuals with type 2 diabetes are more likely to be associated with DR but not in white people [29]. While a meta-analysis from China recognizes the reverse association that rs699947 polymorphism is strongly connected with DR after adjusting for outliers, rs2010963 polymorphism may not be linked to DR [30]. Different meta-analyses on rs2010963; one revealed an association while the other did not [31,32].
The effect of stiffened diabetic red blood cells on wall shear stress in a reconstructed 3D microaneurysm
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2022
Benjamin Czaja, Jonathan de Bouter, Morgan Heisler, Gábor Závodszky, Sonja Karst, Marinko Sarunic, David Maberley, Alfons Hoekstra
Hemodynamic changes have been found to influence the progression of proliferative DR (Klein and Klein 2002; Hennis et al. 2003; Tarr et al. 2010). Specifically, elevated levels of vascular endothelial growth factor (VEGF) have been connected with diabetic retinopathy (Adamis et al. 1994; Caldwell et al. 2003) by inducing vessel permeability (Mathews et al. 1997) and the formation of new blood vessels (Aiello et al. 1995b; Hoeben et al. 2004). The pathophysiology of DR includes the thickening of the vascular basement membrane (Roy et al. 2010) which affects oxygen transport to the retina and leads to secondary VEGF production, which has been found to be induced in response to tissue hypoperfusion (hypoxia/ischemia) (Aiello et al. 1994, 1995a; Gupta et al. 2013). Expression of VEGF by the endothelial cells has also been found to be stimulated by hemodynamic shear stresses on the vessel wall (Ballermann et al. 1998; Shay-Salit et al. 2002; Dela Paz et al. 2012), especially the increase of wall shear stress (WSS) has been identified to cause endothelial dysfunction (Kohner 1993). Studying the influence of whole blood flow on WSS patterns in the retinal micro-vascualature may help the understanding of the increased amounts of VEGF in diabetic retinopathy.
Enhanced osteogenesis and angiogenesis by PCL/chitosan/Sr-doped calcium phosphate electrospun nanocomposite membrane for guided bone regeneration
Published in Journal of Biomaterials Science, Polymer Edition, 2019
Huilin Ye, Junjin Zhu, Dan Deng, Shue Jin, Jidong Li, Yi Man
BMSCs were cultured on three electrospun membranes to analyze the secretion of VEGF, which reflects the angiogenic differentiation (Figure 8). Cells on Sr-CaP/PCL/CS membranes presented highest VEGF expression level with statistical difference as compared with that on PCL/CS membranes, but no significant difference when compared with CaP/PCL/CS membranes. The amount of VEGF was also significant elevated in CaP/PCL/CS group than PCL/CS group. VEGF acts early in vessel formation, which promotes proliferation, migration and maturation of vascular endothelial cells. Zhang et al. [69] verified that Sr ions significantly promoted VEGF expression in canine BMSCs. Wang et al. [70] also indicated the synergistic effects of Ca, Si and Sr ions on stimulating angiogenesis for adipose derived stem cells. Literatures above confirm our results that Sr ions promoted angiogenesis differentiation of BMSCs. Additionally, Preethi et al. [71] found Sr ions in high-dosage was cytotoxic to ST-2 cells (a bone marrow stromal cell line), on the contrary, Sr2+ with low-dosage significantly enhanced cells VEGF secretion. There is no significant difference between CaP/PCL/CS group and Sr-CaP/PCL/CS group in our results, which might call for a higher concentration of Sr ions to improve further the angiogenesis induction ability.