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

Youqiang Fang,Fei Yang,Yun Luo,Shudong Lin,Jie Situ,Shaoxiong Lin

doi:10.1155/2020/9186583

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.

Highlights

Despite the recent advances in prostate cancer therapy, such as improved surgical strategies and new drugs in androgen deprivation therapy, the clinical prognosis of patients diagnosed with castration-resistant prostate cancer (CRPC) remains poor [1, 2]
To avoid the incidence of postsynthesis NP surface modification, the prefunctionalized biointegrated block copolymer that contains all of the three desired NP components was firstly developed. e PLGA-b-PEG3.4k-bWy5a triblock copolymer was synthesized by a two-step reaction (Figure 1)
Multifunctional polymeric nanoparticles were synthesized for tumor-targeted intracellular drug release and magnetic resonance imaging (MRI). e prostate cancer specific aptamer Wy5a was introduced on the nanoparticle surface as a targeting moiety, which has been developed for CRPC cell line PC-3 by cell-SELEX technique in our previous study [12]

Summary

Introduction

Despite the recent advances in prostate cancer therapy, such as improved surgical strategies and new drugs in androgen deprivation therapy, the clinical prognosis of patients diagnosed with castration-resistant prostate cancer (CRPC) remains poor [1, 2]. Docetaxel (Dtxl) has been widely used as the first-line chemotherapeutic drug for CRPC and showed a survival advantage [1]. The therapeutic efficacy of Dtxl can be compromised by its nonselective toxicity and propensity to induce drug resistance [3]. E improvement in multifunctional nanoparticle technology for combined targeted drug delivery and tumor imaging provides new opportunities to overcome these obstacles [5]. It has been reported that stable GO-coated Fe3O4 nanocomposites are successfully used as a robust drug delivery carrier for simultaneous tumor MR imaging and targeted therapy [5]. The innovative contrast agents for tumor imaging such as ultrasmall bimetallic bovine serum albumin-directed gold-silver (AuAg@BSA) nanoparticles have attracted significant attention for potential applications in the fields of multifunctional nanomedicine [6]

Results

Discussion

Conclusion