Synthesis of a bi-functional dendrimer-based nanovehicle co-modified with RGDyC and TAT peptides for neovascular targeting and penetration

International Journal of Pharmaceutics
Jing-jing LiKaoxiang Sun

Abstract

The dual-ligand dendritic polyamidoamine-(polyethylene glycol)n-cyclic RGDyC peptide-(TAT peptide) (PPnR(T)) with various supplied molar ratios of polyethylene glycol (PEG) to polyamidoamine (PAMAM) (n=5, 15, 30) were designed as drug-carriers for the treatment of neovascular diseases; their targeting and penetrating effects were subsequently evaluated. (1)H NMR demonstrated PPnR(T) was successfully synthesized. Compared with the unmodified PAMAM, in vitro cytotoxicity of PPnR(T) to αvβ3 negative cells (αvβ3-) was significantly reduced, whereas the lethality to pathologic neovascular endothelial cells (αvβ3+) was efficiently increased compared to PPn. Compared to PP5R(T) and PP15R(T), PP30R(T) exhibited the most selective and efficient cellular uptake by human umbilical vein endothelial cells (HUVECs, αvβ3+). Membrane interaction study indicated the cellular uptake process of PP30R(T) of HUVECs mainly involved specific RGD-αvβ3 recognition as well as electrostatic interactions. Intracellular localization results confirmed PP30R(T) was distributed in the cytoplasm in HUVECs. 3D tumor spheroids penetration studies demonstrated that PP30R(T) penetrated the A549 cells to reach the depths of the avascular tumor spheroids. In vivo im...Continue Reading

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Citations

Apr 20, 2016·Journal of Controlled Release : Official Journal of the Controlled Release Society·Meng WangKaoxiang Sun
May 28, 2016·International Journal of Molecular Sciences·Gitanjali SharmaJagdish Singh
Jan 27, 2017·Bioconjugate Chemistry·Dirk van den BrandWouter P R Verdurmen
May 9, 2018·Journal of Drug Targeting·K R GajbhiyeJ M Gajbhiye
Nov 24, 2019·International Journal of Molecular Sciences·Yu SakuraiHideyoshi Harashima

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