查找使用阿拉丁产品的科研文献

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

Jingjing Li,Xuemei Zhang,Meng Wang,Xuejuan Li,Hongjie Mu,Aiping Wang,Wanhui Liu,Youxin Li,Zimei Wu,Kaoxiang Sun

The dual-ligand dendritic polyamidoamine-(polyethylene glycol) n -cyclic RGDyC peptide-(TAT peptide) (PP n R(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 PP n R(T) was successfully synthesized. Compared with the unmodified PAMAM, in vitro cytotoxicity of PP n R(T) to αvβ3 negative cells (αvβ3-) was significantly reduced, whereas the lethality to pathologic neovascular endothelial cells (αvβ3+) was efficiently increased compared to PP n . Compared to PP 5 R(T) and PP 15 R(T), PP 30 R(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 PP 30 R(T) of HUVECs mainly involved specific RGD-αvβ3 recognition as well as electrostatic interactions. Intracellular localization results confirmed PP 30 R(T) was distributed in the cytoplasm in HUVECs. 3D tumor spheroids penetration studies demonstrated that PP 30 R(T) penetrated the A549 cells to reach the depths of the avascular tumor spheroids. In vivo imaging further demonstrated that PP 30 R(T) achieved profoundly improved distribution in tumor tissues where angiogenesis existed. Therefore, the bi-functional dendrimer PP 30 R(T) displayed great potential as a nano-carrier for targeted drug delivery both in vitro and in vivo , and had broad prospects as nanocarriers for the targeted treatment of neovascular diseases.