Dual-aptamer-based delivery vehicle of doxorubicin to both PSMA (+) and PSMA (-) prostate cancers

摘要

We have designed a dual-aptamer complex specific to both prostate-specific membrane antigens (PSMA) (+) and (-) prostate cancer cells. In the complex, an A10 RNA aptamer targeting PSMA (+) cells and a DUP-1 peptide aptamer specific to PSMA (-) cells were conjugated through streptavidin. Doxorubicin loaded onto the stem region of the A10 aptamer was delivered not only to PSMA (+) cells but to PSMA (-) cells, and eventually induced apoptosis in both types of prostate cancer cells. Furthermore, both aptamers were immobilized onto the TCL-SPION for the in vivo application of the dual-aptamer-based drug delivery system. Doxorubicin was selectively passed into both types of prostate cancer cells due to the specificity of the dual-aptamer probe. This indicates that targeted drug delivery to prostate cancer cells successfully occurred using the drug-loaded aptamer complex via streptavidin and the probe using nanoparticles. In particular, dual-aptamer nanoparticles can be applied as an active drug delivery vector in vivo for the general targeting of both types of prostate cancer, including the PSMA (-) cell line, due to the particles' suitability for use as MR contrast agents.