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

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.

Nanoparticle Activation Methods in Cancer Treatment

“…Polymer microbubbles have also been formulated which contain doxorubicin. In the latter, the drug is encapsulated using an emulsion method, and when the shell is ruptured by ultrasound irradiation the drugs are released into the tissue [39,79]. While it was successful, only a low loading capacity of doxorubicin in the bubbles was achieved and so the system was adapted to encapsulate the very potent microtubule stabilizing drug paclitaxel [42,79].…”

“…This raises the possibility for enzymes to activate nanoparticle systems specifically at the tumour site [29,31]. A number of cellular enzymes have been used in enzymatic activation systems, including cathepsins [32,33], matrix metallo-proteinases (MMP) [33,34], hyaluronidase (HAase) [35], glycosyl hydrolases [36], NAD(P)H-quinone oxidoreductase-1 (NQO1) [30,37], protein tyrosine kinase-7 (PTK-7) [38], and telomerase [29,39].…”

“…Very recently, Shi et al developed a unique telomerase activity-triggered DOX release theranostic nanoprobe [39]. Telomerase activity is much higher in cancerous cells than in normal cells.…”

“…As the telomerase activity in cancerous cells is much higher than the normal cells, the elongation of the 3’ region would cause the deconstruction of the aptamer structure and lead to the release of the anticancer DOX and fluorescent 5-carboxyfluorescein (FAM) label which was bundled inside the aptamer. Using MTT assays the nanoprobe was shown to decrease the growth of HeLa cells by over 50%, compared with almost no decrease in the viability of control L-02 cells [39].…”

pH and Redox Dual-Responsive MSN-S-S-CS as a Drug Delivery System in Cancer Therapy

“…So far, several materials, such as inorganic nanoparticles [16,17], dendrimers [18,19], rotaxane [20], cyclodextrin [21] and DNA [22] have been applied to cap the mesoporous openings on the surface of MSN. These materials permit different external triggering motifs such as redox state changes [23], pH [24], temperature [25], illumination [26], enzyme activity [27] and so on to achieve a controlled release of guest drugs from the pores. However, the side effects of these cancer therapeutics cannot be ignored in clinical practice [28].…”