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• W2000403276 abstract "Abstract The overexpression of α v β 3 integrin receptors on tumor cells and tumor vascular endothelium makes it a useful target for imaging, chemotherapy and anti‐angiogenic therapy. However integrin‐targeted delivery of therapeutics by nanoparticles have provided only marginal, if any, enhancement of therapeutic effect. This work was thus focused on the development of novel α v β 3 ‐targeted near infrared light‐emitting solid lipid nanoparticles (SLN) through conjugation to the α v β 3 integrin‐specific ligand cyclic Arg‐Gly‐Asp (cRGD), and the assessment of the effects of α v β 3 targeting on nanoparticle biodistribution. Since our previously developed non‐targeted “stealth” SLN showed little hepatic accumulation, unlike most reported liposomes and micelles, they served as a reference for quantifying the effects of cRGD‐conjugation on tumor uptake and whole animal biodistribution of SLN. Non‐targeted SLN, actively targeted (RGD‐SLN) and blocked RGD‐SLN were prepared to contain near infrared quantum dots for live animal imaging. They were injected intravenously to nude mice bearing xenograft orthotopic human breast tumors or dorsal window chamber breast tumors. Tumor micropharmacokinetics of various SLN formulations were determined using intravital microscopy, and whole animal biodistribution was followed over time by optical imaging. The active tumor targeting with cRGD was found to be a “double‐edged sword”: while the specificity of RGD‐SLN accumulation in tumor blood vessels and their tumor residence time increased, their distribution in the liver, spleen, and kidneys was significantly greater than the non‐targeted SLN, leaving a smaller amount of nanoparticles in the tumor tissue. Nevertheless the enhanced specificity and retention of RGD‐SLN in tumor neovasculature could make this novel formulation useful for tumor neovascular‐specific therapies and imaging applications." @default.
• W2000403276 created "2016-06-24" @default.
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• W2000403276 date "2012-07-25" @default.
• W2000403276 modified "2023-10-12" @default.
• W2000403276 title "A Novel Solid Lipid Nanoparticle Formulation for Active Targeting to Tumor α_vβ₃Integrin Receptors Reveals Cyclic RGD as A Double-Edged Sword" @default.
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• W2000403276 doi "https://doi.org/10.1002/adhm.201200006" @default.
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