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

Abstract

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.

The Value of Convolutional Neural Network-Based Magnetic Resonance Imaging Image Segmentation Algorithm to Guide Targeted Controlled Release of Doxorubicin Nanopreparation

“…The results of this study showed that compared with the traditional CNN MRI image segmentation effect, the upgraded 3D CNN-based MRI image segmentation effect was better, with significant improvement in the accuracy, sensitivity, and specificity indicators, and the differences were all statistically marked ( p < 0.05). This was similar to the research results of Fang et al [ 19 ], indicating that the image segmentation algorithm based on CNN could improve the quality of MRI images very well. In the monitoring of the targeted drug therapy of doxorubicin nanopreparations for liver cancer patients, it was found that the MRI images of liver cancer patients processed by a 3D CNN-based MRI image segmentation algorithm could be more intuitively observed and guided to accurately arrive at the target of liver cancer to accurately kill liver cancer cells and optimize the targeted therapy process of liver cancer.…”

Biopolymer and Biomaterial Conjugated Iron Oxide Nanomaterials as Prostate Cancer Theranostic Agents: A Comprehensive Review

“…Xenograft model for in vivo analysis also showed inhibitory effect against tumor with normal level of white blood cell (WBC) count. So this nanoformulation showed enhanced efficacy of CRPC theranostic and low toxicity to the circulation both in vivo and in vitro that make it promising drug delivery system for the efficient treatment of CRPC [120].…”

“…However, DTX became resistant to cancer therapeutics, as mentioned earlier [108]. Both of these limitations can be removed by a nanoscopic therapeutic system through the formulation of Wy5a-DTX-SPION [120]. In this nanoformulation, SPION were encapsulated by DTX and Wy5a aptamer directed the transport of nanoparticles to the targeted cancer cells.…”

Advances in Medical Imaging: Aptamer- and Peptide-Targeted MRI and CT Contrast Agents

“…It is evident that multifunctional formulations like this one are a promising class of targeted drug and contrast delivery systems. 27 …”