A chirality/microRNA dual-gating theranostic nanomachine for gene silencing therapy

DNAzyme-based gene silencing is a promising cancer therapy technology, while its efficiency and safety issues still need to be addressed. In this study, we developed a chirality/microRNA dual-gating theranostic nanomachine for messenger RNA (mRNA) gene silencing therapy with enhanced targeting towards human cervical cancer (HeLa) cells. The chiral nanoparticle, an emerging material with unique chirality-induced properties, e.g. chirality-dependent cellular uptake, has been widely applied in biomedical fields. The L-type gold nanoparticles (L-AuNPs) are used as the nanocarrier with the first “chirality-gating”. L-AuNPs showed 2.4-fold uptake efficiency for HeLa cells comparing to normal cell, as well as 2.2-fold uptake efficiency in cancer cell comparing to D-type gold nanoparticles (D-AuNPs), which exhibited no cancer cell targeting effect. Moreover, an entropy-driven-DNAzyme (EDz) circuit that can release numerous DNAzyme and fluorescence probes with the trigger of single microRNA (miRNA) conducted the theranostic role of both miRNA imaging and gene silencing, constituting the second “miRNA gating”. Ascribing to the prominent targeting nanocarrier L-AuNPs, the miRNA imaging sensitivity and gene silencing therapy efficiency were improved by 2.6- and 5.0-fold, respectively, comparing to those by D-AuNPs. In general, this dual-gating nanomachine, designed with a powerful yet simple strategy, has showed great prospects in optimizing delivery specificity and avoiding off-target toxicities.