当前位置： SCI文献检索 > INTERNATIONAL JOURNAL OF PHARMACEUTICS期刊下所有文献 > Synthesis of a bi-functional dendrimer-based nanovehicle co-modified with RGDyC and TAT peptides for neovascular targeting and penetration.

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

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 imaging further demonstrated that PP30R(T) achieved profoundly improved distribution in tumor tissues where angiogenesis existed. Therefore, the bi-functional dendrimer PP30R(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.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Li J,Zhang X,Wang M,Li X,Mu H,Wang A,Liu W,Li Y,Wu Z,Sun K

doi

10.1016/j.ijpharm.2016.01.068

subject

Has Abstract

pub_date

2016-03-30 00:00:00

pages

112-23

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(16)30068-0

journal_volume

501

pub_type

杂志文章

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