Molecular imaging of telomerase and the enzyme activity-triggered drug release by using a conformation-switchable nanoprobe in cancerous cells

Hai Shi,Liu Shi,Genxi Li,Yang Xiang,Tianshu Chen,Tao Gao,Yuanyang Li

doi:10.1038/s41598-018-34670-7

Hai Shi, Liu Shi + Show 5 more

Open Access

https://doi.org/10.1038/s41598-018-34670-7

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Abstract

So far, the development of a unique strategy for specific biomolecules activity monitoring and precise drugs release in cancerous cells is still challenging. Here, we designed a conformation-switchable smart nanoprobe to monitor telomerase activity and to enable activity-triggered drug release in cancerous cells. The straightforward nanoprobe contained a gold nanoparticle (AuNP) core and a dense layer of 5-carboxyfluorescein (FAM)-labeled hairpin DNA shell. The 3′ region of hairpin DNA sequence could function as the telomerase primer to be elongated in the presence of telomerase, resulting in the conformational switch of hairpin DNA. As a result, the FAM fluorescence was activated and the anticancer drug doxorubicin (Dox) molecules which intercalated into the stem region of the hairpin DNA sequence were released into cancerous cells simultaneously. The smart method could specifically distinguish cancerous cells from normal cells based on telomerase activity. It also showed a good performance for monitoring telomerase activity in the cytoplasm by molecular imaging and precise release of Dox triggered by telomerase activity in cancerous cells. These advantages may offer a great potential of this method for monitoring telomerase activity in cancer progression and estimating therapeutic effect.

Highlights

In dividing cancerous cells, telomerase maintains genome integrity by adding repetitive DNA sequences (TTAGGG) to the chromosome ends
We proposed a straightforward method by using a conformation-switchable smart nanoprobe for telomerase imaging in cancerous cells and telomerase activity-responsive Dox release
As the most direct effect, the quenched FAM was lighted up and the trapped Dox molecules were released into cancerous cells for specific telomerase activity monitoring and precise Dox release

Summary

Introduction

Telomerase maintains genome integrity by adding repetitive DNA sequences (TTAGGG) to the chromosome ends. To obtain the optimal imaging results, the AuNP-MPs were incubated with HeLa cells for different time periods. The distinguishing fluorescence intensity between cancerous and noncancerous cells signified that the AuNP-MPs were successfully lighted up because of the DNA conformational switch induced by telomerase activity in cancerous cells.

Results

Conclusion