These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: cRGD/TAT Dual-Ligand Reversibly Cross-Linked Micelles Loaded with Docetaxel Penetrate Deeply into Tumor Tissue and Show High Antitumor Efficacy in Vivo.
    Author: Zhu Y, Zhang J, Meng F, Deng C, Cheng R, Feijen J, Zhong Z.
    Journal: ACS Appl Mater Interfaces; 2017 Oct 18; 9(41):35651-35663. PubMed ID: 28952305.
    Abstract:
    The application of cell-penetrating peptides like TAT for in vivo targeted delivery is limited because the penetration behavior is not cell-specific. Herein, we designed cRGD and TAT comodified cross-linkable micelles (cRGD/TAT CMs), in which the TAT peptide was shielded by relatively long poly(ethylene glycol) (PEG) chains. Docetaxel (DTX)-loaded cRGD/TAT CMs were very stable with minimal drug leakage under physiological conditions, whereas rapid DTX release took place in a reductive environment. Flow cytometry showed that the cRGD/TAT CMs with molar ratios of 20% cRGD and 10% TAT (cRGD20/TAT10 CMs) were selectively and efficiently taken up by ανβ3-overexpressing U87MG glioma cells, with 8.3-fold and 18.3-fold higher uptake than cRGD20 CMs and PEG CMs, respectively. DTX-loaded cRGD20/TAT10 CMs exhibited a high cytotoxicity in U87MG cells, leading to rapid apoptosis of the tumor cells. Uptake mechanism studies revealed that cRGD20/TAT10 CMs mainly employed the caveolae-mediated endocytotic pathway and efficiently escaped from the lysosomes. Notably, cRGD20/TAT10 CMs had a long circulating time of 6.25 h in vivo, due to cross-linking of the micelles and shielding of the TAT peptide. Moreover, DTX-loaded cRGD20/TAT10 CMs exhibited a significantly higher accumulation and deeper penetration in subcutaneous U87MG glioma tissue compared to cRGD20 CMs and PEG CMs, leading to superior antitumor efficacy in vivo. Therefore, this dual-ligand strategy provides an effective way to realize tumor-specific penetration and inhibition.
    [Abstract] [Full Text] [Related] [New Search]