Aptamer-Functionalized Dendrimer Delivery lncRNA MEG3 Enhances Castration-Resistant Prostate Cancer Gene Therapy

Abstract Androgen castration therapy is an effective treatment method for prostate cancer patients who cannot be completely cured by surgery. However, drug resistance often leads to treatment failure and poor prognosis. For castration-resistant prostate cancer (CRPC), some new treatment methods have been gradually put into clinical validation or use. Considering the side effects of traditional treatment, gene therapy has been applied in recent studies to combat prostate cancer (PCa). A 19-nt RNA aptamer, termed as EpDT3, is endocytosed when bound to epithelial cell adhesion molecule EpCAM-overexpressing cells, including various types of prostate cancer cells. Therefore, poly (amidoamine) dendrimer (PAMAM) conjugated with EpDT3 on the surface was developed for gene delivery targeting the CRPC. Moreover, the PAMAM-PEG-EpDT3 vehicles were accumulated in CRPC cells. The CRPC-inhibitory effect of PAMAM modified with EpDT3 was significantly higher than that of the unmodified construct when loading the plasmid that encodes long noncoding (lnc) RNA MEG3 (pMEG3). In summary, the above results suggested that PAMAM-PEG-EpDT3/pMEG3 nanoparticles (NPs) have great potential for enhancing CRPC gene therapy.