A d -Peptide Ligand of Integrins for Simultaneously Targeting Angiogenic Blood Vasculature and Glioma Cells

Yachao Ren, Changyou Zhan, Jie Gao, Mingfei Zhang, Xiaoli Wei, Man Ying, Zining Liu, Weiyue Lu

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14 Citations (Scopus)


The current prognosis of glioma patients remains poor after intensive multimodal treatments, which is partially due to the existence of the blood-brain tumor barrier (BBTB). In the present study, a novel "bifunctional ligand" (termed D VS) was developed by retro-inverso isomerization. D VS is a ligand of integrins highly expressed on glioma cells and tumor neovasculature. D VS exhibited exceptional stability in serum and demonstrated significantly higher targeting efficiency for glioma and HUVEC cells compared with the parent L-peptide. As a result, D VS modified micelles ( D VS-MS) exhibited high encapsulation efficiency of doxorubicin, ideal size distribution, and sustained release behavior of the payload. In vivo studies showed that D VS-MS could target and efficiently deliver fluorescence to tumor cells and tumor vasculature not only in the mice bearing subcutaneous tumors but also in those bearing intracranial tumors. Moreover, doxorubicin loaded D VS modified micelles exerted potent tumor growth inhibitory activity against subcutaneous and intracranial human glioma in comparison to drug loaded plain micelles and L VS modified micelles. Therefore, D VS appears to be a suitable targeting ligand with potential applications for glioma targeted drug delivery.

Original languageEnglish
Pages (from-to)592-601
Number of pages10
JournalMolecular Pharmaceutics
Issue number2
Publication statusPublished - Feb 2018
Externally publishedYes


  • VS
  • active targeting
  • glioma
  • micelle
  • tumor angiogenic vessels

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