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• W4386269761 endingPage "115780" @default.
• W4386269761 startingPage "115780" @default.
• W4386269761 abstract "E-selectin, which is highly expressed in vascular endothelial cells near tumor and get involved in the all tumor growth steps: occurrence, proliferation and metastasis, is considered as a promise targeted protein for antitumor drug discovery. Herein, we would like to report the design, preparation and the anticancer evaluation of the peptide-PEG-podophyllotoxin conjugate(PEG-Pep-PODO), in which the short peptide (CIELLQAR) was used as the E-selectin ligand for the targeting purpose and the PEG portion the molecule got the conjugate self-assembled to form a water soluble nanoparticle. In vitro release study showed that the conjugated and entrapped PODO could be released simultaneously in the presence of GSH (highly expressed in tumor environmental conditions) and the GSH would catalyze the break of the disufur bond which linked of the PODO and the peptide-PEG portion of the conjugate. Cell adhesion test of the PEG-Pep-PODO indicated that E-selectin ligand peptide CIELLQAR could get specifically and efficiently binding to the E-selectin expressing human umbilical vein endothelial cells (HUVEC). In vitro cytotoxicity assay further revealed that PEG-Pep-PODO significantly improved the selectivity of PEG-Pep-PODO for killing the tumor cells and normal cells compared with PODO solution formulation. More importantly, the in vivo experiment demonstrated that the conjugate would accumulate of the PODO payload in tumor through targeting endothelial cells in the tumor microenvironment, which resulted in the much improved in vivo inhibition of tumor growth, intratumoral microvessel density, and decreased systemic toxicity of this nanoparticle over the free PODO. Furthermore, this water soluble conjugate greatly improved the pharmacokinetic properties of the mother molecule." @default.
• W4386269761 created "2023-08-31" @default.
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• W4386269761 date "2023-11-01" @default.
• W4386269761 modified "2023-10-14" @default.
• W4386269761 title "Podophyllotoxin-Loaded PEGylated E-selectin peptide conjugate targeted cancer site to enhance tumor inhibition and reduce side effect" @default.
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• W4386269761 doi "https://doi.org/10.1016/j.ejmech.2023.115780" @default.
• W4386269761 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37666045" @default.
• W4386269761 hasPublicationYear "2023" @default.
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