AMP-guided tumour-specific nanoparticle delivery via adenosine A1 receptor
| Autor: | Na Li, Yuanxing Zhang, Hua Zhang, Tongcheng Dai, Qin Liu, Fajun Han |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Adenosine monophosphate Polymers Biophysics Mice Nude Bioengineering Breast Neoplasms 02 engineering and technology Biology Fluorescence Biomaterials 03 medical and health sciences chemistry.chemical_compound Adenosine A1 receptor Drug Delivery Systems In vivo Cell Line Tumor medicine Animals Humans Mice Inbred BALB C HEK 293 cells Cancer 021001 nanoscience & nanotechnology medicine.disease Adenosine Xenograft Model Antitumor Assays In vitro Adenosine Monophosphate 030104 developmental biology HEK293 Cells chemistry Biochemistry Mechanics of Materials Cancer cell Colonic Neoplasms Ceramics and Composites Cancer research Nanoparticles Female 0210 nano-technology medicine.drug |
| Zdroj: | Biomaterials. 83 |
| ISSN: | 1878-5905 |
| Popis: | Active targeting-ligands have been increasingly used to functionalize nanoparticles for tumour-specific clinical applications. Here we utilize nucleotide adenosine 5'-monophosphate (AMP) as a novel ligand to functionalize polymer-based fluorescent nanoparticles (NPs) for tumour-targeted imaging. We demonstrate that AMP-conjugated NPs (NPs-AMP) efficiently bind to and are following internalized into colon cancer cell CW-2 and breast cancer cell MDA-MB-468 in vitro. RNA interference and inhibitor assays reveal that the targeting effects mainly rely on the specific binding of AMP to adenosine A1 receptor (A1R), which is greatly up-regulated in cancer cells than in matched normal cells. More importantly, NPs-AMP specifically accumulate in the tumour site of colon and breast tumour xenografts and are further internalized into the tumour cells in vivo via tail vein injection, confirming that the high in vitro specificity of AMP can be successfully translated into the in vivo efficacy. Furthermore, NPs-AMP exhibit an active tumour-targeting behaviour in various colon and breast cancer cells, which is positively related to the up-regulation level of A1R in cancer cells, suggesting that AMP potentially suits for more extensive A1R-overexpressing cancer models. This work establishes AMP to be a novel tumour-targeting ligand and provides a promising strategy for future diagnostic or therapeutic applications. |
| Databáze: | OpenAIRE |
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