Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to develop polymeric nanospheres (NPs) that are able to selectively target the activated vascular endothelium and to deliver co-encapsulated anti-angiogenic agents for improved treatment efficacy in inflammatory diseases with an angiogenic component. We evaluated a novel poly(d,l)-lactide (PLA)-based polymer, grafted with a synthetic ligand specific for selectin (PLA-g-SEL), for the preparation of functionalized NPs. The NPs were produced according to a double emulsion-solvent diffusion/evaporation method, allowing the co-encapsulation of hydrophilic and lipophilic drugs. Incorporation of the functionalized polymer enhanced the internalization of fluorescein-labeled NPs by lipopolysaccharide-activated vascular endothelial cells relative to control NPs, as evidenced by confocal laser scanning microscopy and quantitative fluorescence measurements. Two anti-angiogenic agents, endostatin and paclitaxel, were co-loaded in the functionalized NPs. Respective drug loadings were optimized by adjusting polymer composition, as well as by the microemulsion technique. NPs loaded with either of the chosen drugs or with a combination of them were tested for their anti-angiogenic efficacy in human umbilical vascular endothelial cell (HUVEC) culture in vitro and rat aorta tissue culture ex vivo models. An enhanced anti-proliferative effect on HUVECs and heightened anti-angiogenic action on rat aorta ring cultures was observed for the loaded drugs compared to the free molecules. Moreover, combined loaded treatments were found to be more potent, evoking additive and even synergetic outcomes (at lower doses) greater than the corresponding single-loaded treatments in inhibiting new vessels sprouting in rat aortic rings.
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PMID:Functionalized nanospheres loaded with anti-angiogenic drugs: cellular uptake and angiosuppressive efficacy. 1946 78

Endostar, a novel recombinant human endostatin, has been proven to inhibit tumor angiogenesis and is utilized as an anticancer drug. While free drugs can display limited efficacy, nanoscaled anticancer drugs have been fabricated and proven to possess superior therapeutic effects. Poly(lactic acid) (PLA) is a FDA-approved biomaterial displaying excellent biocompatibility and low toxicity. In this study, Endostar-loaded PLA nanoparticles (EPNPs) were first prepared, and a near-infrared (NIR) dye, IRDye 800CW, was conjugated to the surface for detecting nanoparticle biodistribution through fluorescence molecular imaging (FMI) using an orthotopic breast tumor mouse model. The antitumor efficacy of EPNPs was examined using bioluminescence imaging (BLI) and immunohistology. To further improve the antitumor effects, we combined EPNPs with zoledronic acid monohydrate (ZA), which is known to decrease the tumor-associated macrophages (TAM) and inhibit tumor progression. We found that EPNPs decreased human umbilical vein endothelial cell (HUVEC) viability by inhibiting tumor growth gene expression more significantly than free Endostar in vitro. In vivo, EPNPs displayed better tumor growth inhibitory effects compared with free Endostar, and the combination of EPNPs with ZA exhibited more significant antitumor effects. As confirmed by CD31 and CD11b immunohistochemistry, the combination of EPNPs and ZA showed synergistic effects in reducing tumor angiogenesis and TAM accumulation in tumor regions. Taken together, this study presents a novel and effective form of nanoscaled Endostar for the treatment of breast cancer that displays synergistic antitumor effects in combination with ZA.
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PMID:Infra Red Dye and Endostar Loaded Poly Lactic Acid Nano Particles as a Novel Theranostic Nanomedicine for Breast Cancer. 2728 Feb 47