Telomerase Triggered Drug Release Using a SERS Traceable Nanocarrier

Telomerase is an important cancer biomarker and therapeutic target. Here, we present a new stimuli-responsive drug release method, using telomerase as the trigger. To realize this kind of delivery, mesoporous silica nanoparticle with an inner metal core is used as the nanocarrier. The metal core serves as the surface enhanced Raman scattering (SERS) substrate and produces SERS signal for the tracing of the nanocarrier. Drugs are first loaded inside the pores of the nanocarriers. Then these pores are sealed by a special oligonucleotide strand (CAP1), which contains a telomeric repeat complementary sequence and a telomerase substrate primer sequence. The CAP1 strand blocks the pores and excludes possible drug leakage. Telomerase can recognize the TS primer sequence and add tandem telomeric repeats (TE) to the TS primer. Then the elongated TE sequence can hybridize with its complementary sequence, resulting in a hairpin structure which subsequently falls off the nanocarrier, opens the pore and releases the loaded drugs. In this way, drugs can only be released in cancer cells with a high telomerase expression level. This cancer cell specific and SERS traceable nanocarrier has a great potential in improving the therapeutic efficacy as well as the investigation of nanomaterial based drug delivery dynamics.