Aptamer-Conjugated Multifunctional Polymeric Nanoparticles as Cancer-Targeted, MRI-Ultrasensitive Drug Delivery Systems for Treatment of Castration-Resistant Prostate Cancer.

Nanoscopic therapeutic systems that incorporate therapeutic agents, molecular targeting, and imaging capabilities have gained momentum and exhibited significant therapeutic potential. In this study, multifunctional polymeric nanoparticles with controlled drug delivery, cancer-targeted capability, and efficient magnetic resonance imaging (MRI) contrast characteristics were formulated and applied in the treatment of castration-resistant prostate cancer (CRPC). The "core-shell" targeted nanoparticles (NPs) were synthesized by the self-assembly of a prefunctionalized amphiphilic triblock copolymer composed of poly(lactic-co-glycolic-acid) (PLGA), polyethylene glycol (PEG), and the Wy5a aptamer (Apt), which have been screened for targeting the CRPC cell line PC-3 by cell-SELEX technique as described in our previous study. Docetaxel (Dtxl) and a cluster of hydrophobic superparamagnetic iron oxide (SPIO) nanoparticles were simultaneously encapsulated into the targeted nanoparticles. The targeted NPs showed a controlled drug release and an increased contrast-enhanced MRI capability. The presence of Wy5a on the nanoparticle surface resulted in the cancer-targeted delivery to PC-3 cells in vitro and in vivo. In vitro MRI and cytotoxicity studies demonstrated the ultrasensitive MRI and increased cytotoxicity of these targeted NPs. In vivo studies revealed that the targeted NPs exhibited a more efficacious antitumor capability without significant systemic toxicity. Our data suggested that these targeted NPs may be a promising drug delivery system for the efficacious treatment of CRPC.